Impedance devices and methods of using the same to obtain luminal organ measurements

ABSTRACT

Impedance devices and methods of using the same to obtain luminal organ measurements. In at least one embodiment of an impedance device of the present disclosure, the impedance device comprises an elongated body having a distal body end, and a first electrode located along the elongated body at or near the distal body end, the first electrode configured to obtain one or more conductance values within a mammalian luminal organ within an electric field, wherein a measured parameter of the mammalian luminal organ can be calculated based in part upon the one or more conductance values obtained by the first electrode.

PRIORITY

The present patent application a) is related to, and claims the prioritybenefit of, U.S. Provisional Patent Application Ser. No. 61/800,407,filed on Mar. 15, 2013; b) is related to, claims the priority benefitof, and is a continuation-in-part application of, U.S. patentapplication Ser. No. 13/324,222, filed on Dec. 13, 2011, which isrelated to, claims the priority benefit of, and is a continuationapplication of, U.S. patent application Ser. No. 12/098,242, filed onApr. 4, 2008 and issued as U.S. Pat. No. 8,078,274 on Dec. 13, 2011,which is related to, claims the priority benefit of, and is acontinuation-in-part application of, U.S. patent application Ser. No.11/891,981, filed Aug. 14, 2007 and issued as U.S. Pat. No. 8,114,143 onFeb. 14, 2012, which is related to, claims the priority benefit of, andis a divisional application of, U.S. patent application Ser. No.10/782,149, filed Feb. 19, 2004 and issued as U.S. Pat. No. 7,454,244 onNov. 18, 2008, which is related to, claims the priority benefit of, U.S.Provisional Patent Application Ser. No. 60/449,266, filed Feb. 21, 2003,U.S. Provisional Patent Application Ser. No. 60/493,145, filed Aug. 7,2003, and U.S. Provisional Patent Application Ser. No. 60/502,139, filedSep. 11, 2003; and c) is related to, claims the priority benefit of, andis a continuation-in-part application of, U.S. patent application Ser.No. 13/372,573, filed on Feb. 14, 2012, which is related to, claims thepriority benefit of, and is a continuation application of, U.S. patentapplication Ser. No. 11/891,981, filed Aug. 14, 2007 and issued as U.S.Pat. No. 8,114,143 on Feb. 14, 2012, which has the priority referencedabove. The contents of each of these applications and patents are herebyincorporated by reference in their entirety into this disclosure.

BACKGROUND

The disclosure of the present application relates generally to medicaldiagnostics and treatment equipment, and in particular, to devices,systems, and methods for measuring luminal cross-sectional area of bloodvessels, heart valves and other hollow visceral organs.

Coronary Heart Disease

Coronary heart disease is caused by atherosclerotic narrowing of thecoronary arteries. It is likely to produce angina pectoris, heart attackor both. Coronary heart disease caused 466,101 deaths in USA in 1997 andis the single leading cause of death in America today. Approximately, 12million people alive today have a history of heart attack, anginapectoris or both. The break down for males and females is 49% and 51%,respectively. This year, an estimated 1.1 million Americans will have anew or recurrent coronary attack, and more than 40% of the peopleexperiencing these attacks will die as a result. About 225,000 people ayear die of coronary attack without being hospitalized. These are suddendeaths caused by cardiac arrest, usually resulting from ventricularfibrillation. More than 400,000 Americans and 800,000 patientsworld-wide undergo a non-surgical coronary artery interventionalprocedure each year. Although only introduced in the 1990s, in somelaboratories intra-coronary stents are used in 90% of these patients.

Stents increase minimal coronary lumen diameter to a greater degree thanpercutaneous transluminal coronary angioplasty (PTCA) alone according tothe results of two randomized trials using the Palmaz-Schatz stent.These trials compared two initial treatment strategies: stenting aloneand PTCA with “stent backup” if needed. In the Stent Restenosis Study(STRESS) trial, there was a significant difference in successfulangiographic outcome in favor of stenting (96.1% vs. 89.6%).

Intravascular Ultrasound

Currently intravascular ultrasound is the method of choice to determinethe true diameter of the diseased vessel in order to size the stentcorrectly. The term “vessel,” as used herein, refers generally to anyhollow, tubular, or luminal organ, area, or space within a body. Thetomographic orientation of ultrasound enables visualization of the full360° circumference of the vessel wall and permits direct measurements oflumen dimensions, including minimal and maximal diameter andcross-sectional area. Information from ultrasound is combined with thatobtained by angiography. Because of the latticed characteristics ofstents, radiographic contrast material can surround the stent, producingan angiographic appearance of a large lumen, even when the stent strutsare not in full contact with the vessel wall. A large observationalultrasound study after angio-graphically guided stent deploymentrevealed an average residual plaque area of 51% in a comparison ofminimal stent diameter with reference segment diameter, and incompletewall apposition was frequently observed. In this cohort, additionalballoon inflations resulted in a final average residual plaque area of34%, even though the final angiographic percent stenosis was negative(20.7%). These investigators used ultrasound to guide deployment.

However, using intravascular ultrasound as mentioned above requires afirst step of advancement of an ultrasound catheter and then withdrawalof the ultrasound catheter before coronary angioplasty thereby addingadditional time to the stent procedure. Furthermore, it requires anultrasound machine. This adds significant cost and time and more risk tothe procedure.

Aortic Stenosis

Aortic Stenosis (AS) is one of the major reasons for valve replacementsin adult. AS occurs when the aortic valve orifice narrows secondary tovalve degeneration. The aortic valve area is reduced to one fourth ofits normal size before it shows a hemodynamic effect. Because the areaof the normal adult valve orifice is typically 3.0 to 4.0 cm², an area0.75-1.0 cm² is usually not considered severe AS. When stenosis issevere and cardiac output is normal, the mean trans-valvular pressuregradient is generally >50 mmHg. Some patients with severe AS remainasymptomatic, whereas others with only moderate stenosis developsymptoms. Therapeutic decisions, particularly those related tocorrective surgery, are based largely on the presence or absence ofsymptoms.

The natural history of AS in the adult consists of a prolonged latentperiod in which morbidity and mortality are very low. The rate ofprogression of the stenotic lesion has been estimated in a variety ofhemodynamic studies performed largely in patients with moderate AS.Cardiac catheterization and Doppler echocardiographic studies indicatethat some patients exhibit a decrease in valve area of 0.1-0.3 cm² peryear; the average rate of change is 0.12 cm² per year. The systolicpressure gradient across the valve may increase by as much as 10 to 15mmHg per year. However, more than half of the reported patients showedlittle or no progression over a 3-9 year period. Although it appearsthat progression of AS can be more rapid in patients with degenerativecalcific disease than in those with congenital or rheumatic disease, itis not possible to predict the rate of progression in an individualpatient.

Eventually, symptoms of angina, syncope, or heart failure develop aftera long latent period, and the outlook changes dramatically. After onsetof symptoms, average survival is <2-3 years. Thus, the development ofsymptoms identifies a critical point in the natural history of AS.

Many asymptomatic patients with severe AS develop symptoms within a fewyears and require surgery. The incidence of angina, dyspnea, or syncopein asymptomatic patients with Doppler outflow velocities of 4 m/s hasbeen reported to be as high as 38% after 2 years and 79% after 3 years.Therefore, patients with severe AS require careful monitoring fordevelopment of symptoms and progressive disease.

Indications for Cardiac Catheterization

In patients with AS, the indications for cardiac catheterization andangiography are to assess the coronary circulation (to confirm theabsence of coronary artery disease) and to confirm or clarify theclinical diagnosis of AS severity. If echocardiographic data are typicalof severe isolated. AS, coronary angiography may be all that is neededbefore aortic valve replacement (AVR). Complete left- and right-heartcatheterization may be necessary to assess the hemodynamic severity ofAS if there is a discrepancy between clinical and echocardiographic dataor evidence of associated valvular or congenital disease or pulmonaryhypertension.

The pressure gradient across a stenotic valve is related to the valveorifice area and transvalvular flow through Bernoulli's principle. Thus,in the presence of depressed cardiac output, relatively low pressuregradients are frequently obtained in patients with severe AS. On theother hand, during exercise or other high-flow states, systolicgradients can be measured in minimally stenotic valves. For thesereasons, complete assessment of AS requires (1) measurement oftransvalvular flow, (2) determination of the transvalvular pressuregradient, and (3) calculation of the effective valve area. Carefulattention to detail with accurate measurements of pressure and flow isimportant, especially in patients with low cardiac output or a lowtransvalvular pressure gradient.

Problems with Current Aortic Valve Area Measurements

Patients with severe AS and low cardiac output are often present withonly modest transvalvular pressure gradients (i.e., <30 mmHg). Suchpatients can be difficult to distinguish from those with low cardiacoutput and only mild to moderate AS. In both situations, the low-flowstate and low pressure gradient contribute to a calculated effectivevalve area that can meet criteria for severe AS. The standard valve areaformula (simplified Hakki formula which is valve area=cardiacoutput/[pressure gradient]^(1/2)) is less accurate and is known tounderestimate the valve area in low-flow states; under such conditions,it should be interpreted with caution. Although valve resistance is lesssensitive to flow than valve area, resistance calculations have not beenproved to be substantially better than valve area calculations.

In patients with low gradient stenosis and what appears to be moderateto severe AS, it may be useful to determine the transvalvular pressuregradient and calculate valve area and resistance during a baseline stateand again during exercise or pharmacological (i.e., dobutamine infusion)stress. Patients who do not have true, anatomically severe stenosisexhibit an increase in the valve area during an increase in cardiacoutput. In patients with severe AS, these changes may result in acalculated valve area that is higher than the baseline calculation butthat remains in the severe range, whereas in patients without severe AS,the calculated valve area will fall outside the severe range withadministration of dobutamine and indicate that severe AS is not present.

There are many other limitations in estimating aortic valve area inpatients with aortic stenosis using echocardiography and cardiaccatheterization. Accurate measurement of the aortic valve area inpatients with aortic stenosis can be difficult in the setting of lowcardiac output or concomitant aortic or mitral regurgitations.Concomitant aortic regurgitation or low cardiac output can overestimatethe severity of aortic stenosis. Furthermore, because of the dependenceof aortic valve area calculation on cardiac output, any under oroverestimation of cardiac output will cause inaccurate measurement ofvalve area. This is particularly important in patients with tricuspidregurgitation. Falsely measured aortic valve area could causeinappropriate aortic valve surgery in patients who do not need it.

Other Visceral Organs

Visceral organs such as the gastrointestinal tract and the urinary tractserve to transport luminal contents (fluids) from one end of the organto the other end or to an absorption site. The esophagus, for example,transports swallowed material from the pharynx to the stomach. Diseasesmay affect the transport function of the organs by changing the luminalcross-sectional area, the peristalsis generated by muscle, or bychanging the tissue components. For example, strictures in the esophagusand urethra constitute a narrowing of the organ where fibrosis of thewall may occur. Strictures and narrowing can be treated with distension,much like the treatment of plaques in the coronary arteries.

BRIEF SUMMARY

The disclosure of the present application provides for a system formeasuring cross-sectional areas and pressure gradients in luminalorgans. The disclosure of the present application also provides a methodand apparatus for measuring cross-sectional areas and pressure gradientsin luminal organs, such as, for example, blood vessels, heart valves,and other visceral hollow organs.

The present disclosure provides for a system for measuringcross-sectional areas and pressure gradients in luminal organs. Thepresent disclosure also comprises a method and apparatus for measuringcross-sectional areas and pressure gradients in luminal organs, such as,for example, blood vessels, heart valves, and other visceral holloworgans.

In one embodiment, the system comprises an impedance catheter capable ofbeing introduced into a treatment site, a solution delivery source forinjecting a solution through the catheter into the treatment site, aconstant current source enabling the supply of constant electricalcurrent to the treatment site, and a data acquisition system enablingthe measurement of parallel conductance at the treatment site, wherebyenabling calculation of cross-sectional area at the treatment site.

In one embodiment, the catheter further comprises an inflatable balloonalong its longitudinal axis.

In one embodiment, the catheter further comprises a pressure transducernear the distal end of the catheter.

In one approach, a method of measuring the cross-sectional area of atargeted treatment site comprises: introducing an impedance catheterinto a treatment site; providing constant electrical current to thetreatment site; injecting a first solution of first compound; measuringa first conductance value at the treatment site; injecting a secondsolution of a second compound; measuring a second conductance value atthe treatment site; calculating the cross-sectional area of thetreatment site based on the first and second conductance values and theconductivities of the first and second compounds.

In one approach, a method of constructing a three-dimensional model of atreatment site that comprises: introducing an impedance catheter into atreatment site; measuring a first cross-sectional area at a first point;adjusting the position of the catheter; measuring a secondcross-sectional area at a second point, and so on; constructing athree-dimensional model of the treatment site along the longitudinalaxis based on multiple longitudinal cross-sectional area measurements.

According to at least one embodiment of a method for measuring across-sectional area of a targeted treatment site, the method comprisesthe steps of introducing a device into a treatment site; injecting aknown volume of a first solution having a first concentration and afirst conductivity and injecting a known volume of a second solutionhaving a second concentration and a second conductivity at a firstposition of the treatment site; measuring a first treatment siteconductance at the first position of the treatment site; moving thedevice to a second position of the treatment site at a first speed;injecting a known volume of a first solution having a firstconcentration and a first conductivity and injecting a known volume of asecond solution having a second concentration and a second conductivityat the second position of the treatment site; measuring a secondtreatment site conductance at the second position of the treatment site;and calculating cross-sectional areas of the first position and thesecond position of the treatment site.

In another embodiment, the treatment site comprises a site selected fromthe group consisting of a body lumen, a body vessel, a biliary tract,and an esophagus. In yet another embodiment, the treatment sitecomprises an esophagus, and wherein the step of injecting a known volumeof a first solution having a first concentration and a firstconductivity comprises the step of administering said first solution toa patient orally. In an additional embodiment, the first solution isNaCl.

According to at least one embodiment of a method for measuring across-sectional area of a targeted treatment site, the method furthercomprises the step of providing electrical current flow for a period oftime to the treatment site through the device. In another embodiment,the first concentration of the first solution does not equal the secondconcentration of the second solution. In yet another embodiment, thefirst conductivity of the first solution does not equal the secondconductivity of the second solution. In an additional embodiment, themethod further comprises the step of calculating a first nodal voltageand a first electrical field based upon the first treatment siteconductance value and a first current density. In yet an additionalembodiment, the method further comprises the step of applying finiteelement analysis to the first nodal voltage and the first electricalfield, wherein the step of finite element analysis is performed using afinite element software package.

According to at least one embodiment of a method for measuring across-sectional area of a targeted treatment site, the device comprisesa catheter. In another embodiment, the catheter comprises an impedancecatheter. In yet another embodiment, the catheter comprises a guidecatheter.

According to at least one embodiment of a method for measuring across-sectional area of a targeted treatment site, the device comprisesa wire. In another embodiment, the wire comprises an impedance wire. Inyet another embodiment, the wire comprises a wire selected from thegroup consisting of a guide wire, a pressure wire, and a flow wire. Inan additional embodiment, the wire comprises a flow wire, and whereinthe flow wire is operable to measure a velocity of fluid flow.

According to at least one embodiment of a method for measuring across-sectional area of a targeted treatment site, the device comprisesan inflatable balloon positioned along a longitudinal axis of thedevice. In another embodiment, the method further comprises the step ofinflating the balloon to breakup materials causing stenosis at thetreatment site. In yet another embodiment, the device further comprisesa stent located over the balloon, the stent capable of being distendedto a desired size and implanted into the treatment site. In anadditional embodiment, the method further comprises the steps ofdistending the stent by inflating the underlying balloon; and releasingand implanting the stent into the treatment site. In yet an additionalembodiment, the balloon is inflated using a fluid, and the methodfurther comprises the steps of providing electrical current into thefluid filling the balloon at various degrees of balloon distension;measuring a conductance of the fluid inside the balloon; and calculatinga cross-sectional area of the balloon lumen.

According to at least one embodiment of a method for measuring across-sectional area of a targeted treatment site, the method furthercomprises the steps of selecting an appropriately-sized stent based on across-sectional area of the treatment site; and implanting the stentinto the treatment site. In another embodiment, the device comprises apressure transducer. In yet another embodiment, the method furthercomprising the steps of measuring a first pressure gradient from thepressure transducer near the treatment site; and calculating thecross-sectional area of the treatment site based in part on the firstpressure gradient.

According to at least one embodiment of a method for measuring across-sectional area of a targeted treatment site, the step of injectinga known volume of a first solution having a first concentration and afirst conductivity temporarily substantially displaces blood present atthe treatment site. In another embodiment, the first solution is heatedto an internal body temperature of a body surrounding the treatment siteprior to injection. In yet another embodiment, wherein the firstsolution and the second solution are heated to a common temperatureprior to injection. In an additional embodiment, the first volume of thefirst solution is equal to the second volume of the second solution.

According to at least one embodiment of a method for measuring across-sectional area of a targeted treatment site, the step of measuringa first treatment site conductance further comprises the step ofmeasuring a first cross-sectional area, and wherein the step ofmeasuring a second treatment site conductance further comprises the stepof measuring a second cross-sectional area. In another embodiment, themethod further comprises the step of constructing a profile of thetreatment site based in part on the measurements of the firstcross-sectional area and the second cross-sectional area. In yet anotherembodiment, the step of moving the device comprises pulling back thedevice to a second position of the treatment site. In an additionalembodiment, the step of moving the device comprises pushing the deviceforward to a second position of the treatment site.

According to at least one embodiment of a method for measuring across-sectional area of a targeted treatment site, the calculation ofthe cross-sectional areas of the first position and the second positionof the treatment site is based in part upon the first treatment siteconductance, the second treatment site conductance, the firstconductivity of the first solution, and the second conductivity of thesecond solution. In another embodiment, the method further comprises thestep of calculating two Coeff ratios based in part upon the firsttreatment site conductance, the second treatment site conductance, andthe cross-sectional areas of the first position and the second positionof the treatment site. In yet another embodiment, the step of moving thedevice to a second position of the treatment site further comprises thesteps of obtaining one or more additional conductance measurementsbetween the first position and the second position of the treatmentsite; and calculating one or more additional cross-sectional areas basedupon the one or more additional conductance measurements. In anadditional embodiment, the method further comprises the step ofdetermining one or more diameters based in part upon the cross-sectionalareas of the first position and the second position of the treatmentsite and the one or more additional cross-sectional areas based upon theadditional conductance measurements.

According to at least one embodiment of a method for measuring across-sectional area of a targeted treatment site, the method furthercomprises the step of constructing a profile of the treatment site basedupon the one or more diameters. In another embodiment, the methodfurther comprises the step of calculating total conductance for adistance between the first position and the second position of thetreatment site. In yet another embodiment, the method further comprisesthe step of constructing a profile of the treatment site based upon thecross-sectional areas. In an additional embodiment, the step ofinjecting a known volume of a first solution having a firstconcentration and a first conductivity comprises injecting the firstsolution local to the first position of the treatment site.

According to at least one embodiment of a method for measuring across-sectional area of a targeted treatment site, the device comprisesa stent positioned along a longitudinal axis of the device, the stentcapable of being distended to a desired size and implanted into thetreatment site. In another embodiment, the method further comprises thesteps of positioning the stent at or near the treatment site; distendingthe stent; and releasing and implanting the stent into the treatmentsite. In yet another embodiment, the method further comprises the stepof introducing a stent at or near the treatment site, the stent having alength, a collapsed diameter, and a distended diameter. In an additionalembodiment, a stent having a particular length is selected based upon alength of a stenosis. In yet an additional embodiment, the length of thestenosis is determined based upon a profile created in part based uponthe cross-sectional areas of the first position and/or the secondposition of the treatment site.

According to at least one embodiment of a method for measuring across-sectional area of a targeted treatment site, a stent having aparticular collapsed diameter is selected based upon the cross-sectionalareas of the first position and/or the second position of the treatmentsite. In another embodiment, a stent having a particular distendeddiameter is selected based upon the cross-sectional areas of the firstposition and/or the second position of the treatment site. In yetanother embodiment, the first treatment site conductance and the secondtreatment site conductance are retrieved by a data acquisition andprocessing system operably connected to the device, and wherein the dataacquisition and processing system is operable to calculatecross-sectional areas.

According to at least one embodiment of a method for measuring across-sectional area of a targeted treatment site, the device comprisesat least one suction/infusion port in communication with at least onelumen of the device, whereby said injections of solutions occur via theat least one suction/infusion port. In another embodiment, the devicefurther comprises at least one solution delivery source operably coupledto the at least one lumen of the device, whereby the first solution andthe second solution may be injected from the at least one solutiondelivery source through the at least one lumen of the device, throughthe at least one suction/infusion port, and into the treatment site. Inyet another embodiment, the device comprises at least one excitationelectrode and at least one detection electrode. In an additionalembodiment, the at least one excitation electrode comprises a firstexcitation impedance lead, and wherein the at least one detectionelectrode comprises a first detection impedance lead.

According to at least one embodiment of a method for measuring across-sectional area of a targeted treatment site, the treatment sitehas a relative longitudinal axis, and wherein the method furthercomprises the step of constructing a profile along the relativelongitudinal axis of the treatment site based in part on the first andsecond cross-sectional area measurements. In another embodiment, thetreatment site has a relative longitudinal axis, and wherein the step ofmoving the device to a second position of the treatment site furthercomprises the steps of obtaining one or more additional conductancemeasurements between the first position and the second position of thetreatment site; and calculating one or more additional cross-sectionalareas based upon the one or more additional conductance measurements. Inanother embodiment, the method further comprises the step ofconstructing a profile along the relative longitudinal axis of thetreatment site based in part on the first and second cross-sectionalarea measurements and the one or more additional cross-sectional areas.In yet another embodiment, the method further comprises the step ofcomprising the step of determining one or more diameters based in partupon the cross-sectional areas of the first position and the secondposition of the treatment site and the one or more additionalcross-sectional areas based upon the additional conductancemeasurements. In an additional embodiment, the method further comprisesthe step of constructing a profile of the treatment site based upon theone or more diameters.

According to at least one embodiment of a method for measuring across-sectional area of a targeted treatment site, the device comprisesa sensor for measurement of fluid flow. In another embodiment, thedevice is dimensioned so that a first solution can be infusedtherethrough. In yet another embodiment, the data acquisition andprocessing system is operable to receive conductance data from thedevice at a first treatment site, and wherein the data acquisition andprocessing system is further operable to determine the first treatmentsite conductance based in part from the conductance data.

According to at least one embodiment of a method for measuring across-sectional area of a targeted treatment site, the device comprisesa catheter having a lumen, a proximal end, and a distal end, and whereinthe at least one excitation electrode and the at least one detectionelectrode are positioned at or near the distal end of the catheter. Inanother embodiment, the at least one excitation electrode and the atleast one detection electrode have insulated electrical wire connectionsthat run through the lumen and proximal end of the catheter. In yetanother embodiment, the at least one excitation electrode and the atleast one detection electrode have electrical wire connections that areembedded within the catheter such that each wire comprising theelectrical wire connections are insulated from the other wires.

According to at least one embodiment of a method for measuring across-sectional area of a targeted treatment site, the cathetercomprises a lumen extending therethrough, and further comprising a wirepositioned through at least a portion of the lumen of the catheter.

According to at least one embodiment of a method for measuring across-sectional area of a targeted treatment site, the method comprisesthe steps of introducing a device into a treatment site; injecting aknown volume of a first solution having a first concentration and afirst conductivity and injecting a known volume of a second solutionhaving a second concentration and a second conductivity at a firstposition of the treatment site; measuring a first treatment siteconductance at the first position of the treatment site; pulling backthe device to a second position of the treatment site at a first speedwhile injecting a known volume of the second solution, wherein thesecond position is located proximally relative to the first position;injecting a known volume of a first solution having a firstconcentration and a first conductivity at the second position of thetreatment site; measuring a second treatment site conductance at thesecond position of the treatment site; and calculating cross-sectionalareas of the first position and the second position of the treatmentsite based in part upon the first treatment site conductance, the secondtreatment site conductance, the first conductivity of the firstsolution, and the second conductivity of the second solution. In anotherembodiment, the method further comprises the step of constructing aprofile of the treatment site based in part on the measurements of thefirst cross-sectional area and the second cross-sectional area. In yetanother embodiment, the device comprises an inflatable balloon along alongitudinal axis of the device.

According to at least one embodiment of a method for measuring across-sectional area of a targeted treatment site, the method furthercomprises the step of inflating the balloon to breakup any materialscausing stenosis at the treatment site. In another embodiment, thedevice further comprises a stent located over the balloon, the stentcapable of being distended to a desired lumen size and implanted intothe treatment site. In yet another embodiment, the method furthercomprises the steps of distending the stent by inflating the underlyingballoon; and releasing and implanting the stent into the treatment site.In an additional embodiment, the balloon is inflated using a fluid, andthe method further comprises the steps of providing electrical currentinto the fluid filling the balloon at various degrees of balloondistension; measuring a conductance of the fluid inside the balloon; andcalculating a cross-sectional area of the balloon lumen.

According to at least one embodiment of a method for measuring across-sectional area of a targeted treatment site, the method furthercomprises the steps of selecting an appropriately-sized stent based on across-sectional area of the treatment site; and implanting the stentinto the treatment site. In another embodiment, the step of pulling backthe device to a second position of the treatment site further comprisesthe step of obtaining one or more additional conductance measurementsbetween the first position and the second position of the treatment siteand the step of calculating one or more additional cross-sectional areasbased upon the one or more additional conductance measurements. In yetanother embodiment, the method further comprises the step ofconstructing a profile of the treatment site based in part upon thecross-sectional area of the first position and the second position ofthe treatment site and the one or more additional cross-sectional areasbased upon the additional conductance measurements.

According to at least one embodiment of a method for measuring across-sectional area of a targeted treatment site, the method comprisesthe steps of calculating a total conductance based upon individualconductance values taken at a proximal end and a distal end of asegment; calculating two Coeff ratios based upon the total conductanceand the cross-sectional areas of the proximal and the distal end of thesegment; linearly interpolating along a length of pull back of a devicefor the Coeff so that the proximal and the distal end of the segmenthave the same Coeffs as calculated herein; calculating a totalconductance for the length of the pull back; multiplying the totalconductance for the length of the pull back by its respective Coeff forat least one point calculated during pull back to obtain across-sectional area for the at least one point calculated during pullback; and determining the diameter for the at least one point calculatedduring pull back from the cross-sectional area for the at least onepoint calculated during pull back.

In another embodiment, the step of calculating two Coeff ratios isperformed by dividing the two cross-sectional areas by the totalconductance. In yet another embodiment, the step of determining thediameter for the at least one point is determined by multiplying thecross-sectional area of the at least one point by four, dividing theresulting product by pi, and taking the square root of the resultingquotient.

According to at least one embodiment of a method for measuring across-sectional area of a targeted treatment site, the method comprisesthe steps of introducing a device into a treatment site; injecting aknown volume of a first solution having a first concentration and afirst conductivity at a first position of the treatment site; measuringa first conductance at the first position of the treatment site;injecting a known volume of a second solution having a secondconcentration and a second conductivity at a first position of thetreatment site; measuring a second conductance at the first position ofthe treatment site; moving the device to a second position of thetreatment site at a first speed; injecting a known volume of a firstsolution having a first concentration and a first conductivity at thesecond position of the treatment site; measuring a third conductance atthe second position of the treatment site; injecting a known volume of asecond solution having a second concentration and a second conductivityat the second position of the treatment site; measuring a fourthconductance at the second position of the treatment site; andcalculating cross-sectional areas of the first position and the secondposition of the treatment site based in part from the first conductance,the second conductance, the third conductance, and the fourthconductance.

According to at least one embodiment of a method for constructing aprofile of a targeted treatment site, the method comprises the steps ofintroducing a device into a treatment site; injecting a known volume ofa first solution having a first concentration and a first conductivityand injecting a known volume of a second solution having a secondconcentration and a second conductivity at a first position of thetreatment site; measuring a first treatment site conductance at thefirst position of the treatment site; moving the device to a secondposition of the treatment site at a first speed; injecting a knownvolume of a first solution having a first concentration and a firstconductivity and injecting a known volume of a second solution having asecond concentration and a second conductivity at the second position ofthe treatment site; measuring a second treatment site conductance at thesecond position of the treatment site; calculating cross-sectional areasof the first position and the second position of the treatment site; andconstructing a profile of the treatment site based upon thecross-sectional areas of the first position and the second position ofthe treatment site.

In another embodiment, the step of moving the device to a secondposition of the treatment site further comprises the steps of obtainingone or more additional conductance measurements between the firstposition and the second position of the treatment site; and calculatingone or more additional cross-sectional areas based upon the one or moreadditional conductance measurements. In yet another embodiment, themethod further comprises the step of constructing a profile of thetreatment site based upon the cross-sectional areas of the firstposition and the second position of the treatment site and the one ormore additional cross-sectional areas.

According to at least one embodiment of a method for implanting a stentto a targeted treatment site, the method comprises the steps ofintroducing a device into a treatment site; injecting a known volume ofa first solution having a first concentration and a first conductivityand injecting a known volume of a second solution having a secondconcentration and a second conductivity at a first position of thetreatment site; measuring a first treatment site conductance at thefirst position of the treatment site; moving the device to a secondposition of the treatment site at a first speed; injecting a knownvolume of a first solution having a first concentration and a firstconductivity and injecting a known volume of a second solution having asecond concentration and a second conductivity at the second position ofthe treatment site; measuring a second treatment site conductance at thesecond position of the treatment site; calculating cross-sectional areasof the first position and the second position of the treatment site;selecting an appropriately-sized stent based on a cross-sectional areaof the treatment site; and implanting the stent into the treatment site.

The present disclosure also includes disclosure of exemplary unipolar,bipolar, and tetrapolar devices having various components, features,and/or configurations as described herein. The present disclosure alsoincludes disclosure of exemplary unipolar, bipolar, and tripolar methodsusing one or more unipolar, bipolar, and tripolar devices.

The disclosure of the present application includes disclosure ofexemplary unipolar, bipolar, and tripolar devices to perform one or moreof the following procedures/tasks: (a) determining the size(cross-sectional area or diameter, for example) of a mammalian luminalorgan, (b) determining parallel tissue conductance within a mammalianluminal organ, (c) navigation of said device(s) within a luminal organ,(d) determining the location of one or more body lumen junctions withina mammalian luminal organ, (e) determining profiles of a luminal organ,(f) ablating a tissue within a mammalian patient, (g) removing stenoticlesions from a vessel, (h) determining the existence, potential type,and/or vulnerability of a plaque within a luminal organ, (i) determiningphasic cardiac cycle measurements, (j) determining vessel compliance,(k) determining the velocity of a fluid flowing through a mammalianluminal organ, (l) sizing valves using impedance and balloons, such assizing a valve annulus for percutaneous valves, (m) detecting and/orremoving contrast from mammalian luminal organs, (n) determiningfractional flow reserve, and/or (o) placing leads within a mammalianluminal organ.

The present disclosure also includes disclosure of exemplary devices,such as exemplary unipolar, bipolar, tripolar, and tetrapolar devices toperform one or more of the following procedures/tasks: (a) ablation ofrelatively small veins for Endovascular Laser Therapy (EVLT) fortreatment of venous insufficiency of varicose veins and/or othercosmetic procedures, and/or (b) navigation through a portion of apatient's urological system, such as within a ureter, to potentiallyidentify a stenosis or a size abnormality.

In at least one embodiment of an impedance device of the presentdisclosure, the impedance device comprises an elongated body having adistal body end, and a first electrode located along the elongated bodyat or near the distal body end, the first electrode configured to obtainone or more conductance values within a mammalian luminal organ withinan electric field, wherein a measured parameter of the mammalian luminalorgan can be calculated based in part upon the one or more conductancevalues obtained by the first electrode. In another embodiment, the firstelectrode is configured to operate as an excitation electrode and adetection electrode. In yet another embodiment, the first electrode isconfigured to generate the electric field with an external electrodewithin a mammalian body when the external electrode that is not coupledto the elongated body is positioned upon or within the mammalian bodyand when the first electrode and the external electrode are activated.In an additional embodiment, the first electrode is configured to detectthe electric field generated by the first electrode and the externalelectrode.

In at least one embodiment of an impedance device of the presentdisclosure, the impedance device further comprises a second electrodepositioned along the elongated body, wherein the second electrode isconfigured to detect the electric field generated by the first electrodeand the external electrode. In an additional embodiment, the firstelectrode is configured to generate the electric field with a firstexternal electrode within a mammalian body when the first externalelectrode that is not coupled to the elongated body is positioned uponor within the mammalian body and when the first electrode and theexternal electrode are activated. In yet an additional embodiment, thesecond electrode is configured to detect the electric field with asecond external electrode within the mammalian body when the secondexternal electrode that is not coupled to the elongated body ispositioned upon or within the mammalian body. In another embodiment, aknown distance between the first electrode and the second electrode isbetween 0.5 mm and 1 mm, inclusive. In yet another embodiment, a knowndistance between the first electrode and the second electrode is between0.5 mm and 1 mm, inclusive, and wherein the measured parameter is alsocalculated based in part upon the known distance.

In at least one embodiment of an impedance device of the presentdisclosure, the first electrode is configured to generate the electricfield with an external electrode within a mammalian body when theexternal electrode that is not coupled to the elongated body ispositioned upon or within the mammalian body and when the firstelectrode and the external electrode are activated. In anotherembodiment, the device further comprises a second electrode and a thirdelectrode each positioned along the elongated body, the second electrodeand the third electrode configured to detect the electric fieldgenerated by the first electrode and the external electrode.

In at least one embodiment of an impedance system of the presentdisclosure, the system comprises an elongated body having a distal bodyend and a first electrode located along the elongated body at or nearthe distal body end, the first electrode configured to obtain one ormore conductance values within a mammalian luminal organ within anelectric field, and a first external electrode that is not coupled tothe elongated body, wherein a measured parameter of the mammalianluminal organ can be calculated based in part upon the one or moreconductance values obtained by the first electrode within the electricfield generated by the first electrode and the first external electrode.In an additional embodiment, the first electrode and the first externalelectrode are each configured to operate as an excitation electrode anda detection electrode. In yet an additional embodiment, the firstexternal electrode comprises part of device selected from the groupconsisting of a patch, a sheath, and a clip. In another embodiment, thesystem further comprises a second electrode positioned along theelongated body, wherein the second electrode is configured to detect theelectric field.

In at least one embodiment of an impedance system of the presentdisclosure, the system further comprises a second external electrodethat is not coupled to the elongated body, wherein the second electrodeand the second external electrode are configured to detect the electricfield within a mammalian body when the second external electrode ispositioned upon or within the mammalian body. In an additionalembodiment, the system further comprises a third electrode positionedalong the elongated body, wherein the third electrode is configured todetect the electric field with the second electrode.

In at least one embodiment of a method of using an impedance device ofthe present disclosure, the method comprises the steps of introducing atleast part of an impedance device into a mammalian luminal organ at afirst location, the impedance device comprising an elongated body havinga distal body end, and a first electrode located along the elongatedbody at or near the distal body end, the first electrode configured toobtain one or more conductance values within a mammalian luminal organwithin an electric field, providing electrical current to the firstelectrode and a first external electrode not coupled to the elongatedbody to generate the electric field, the first external electrodepositioned upon or within a mammalian body having the mammalian luminalorgan, obtaining at least one conductance value using the impedancedevice within the electric field, and calculating a measured parameterof the mammalian luminal organ based in part upon the at least oneconductance value. In another embodiment, the measured parameter isselected from the group consisting of a luminal organ diameter and aluminal organ cross-sectional area, and wherein the step of obtaining isperformed in the presence of a bolus of an injected fluid having a knownconductivity different than that of blood. In yet another embodiment,the impedance device further comprises a second electrode positionedalong the elongated body, and wherein the step of obtaining the at leastone conductance value is performed using first electrode and the secondelectrode. In an additional embodiment, the impedance device furthercomprises a second electrode and a third electrode each positioned alongthe elongated body, and wherein the step of obtaining the at least oneconductance value is performed using second electrode and the thirdelectrode.

In at least one embodiment of a method of using an impedance device ofthe present disclosure, the step of obtaining at least one conductancevalue is performed within an undiluted bolus of an injected firstsolution having a known conductivity differing from a bloodconductivity, and wherein the step of obtaining the at least anotherconductance value also performed within a bolus selected from theundiluted bolus of the injected first solution and an undiluted bolus ofan injected second solution having a known conductivity differing fromthe blood conductivity. In another embodiment, the step of obtaining isperformed when the first electrode is at a first location within themammalian luminal organ, and wherein the method further comprises thefollowing steps to be performed after the step of obtaining the at leastone conductance value: moving the first electrode of the impedancedevice to a second location within the mammalian luminal organ,obtaining at least another conductance value using the impedance devicewithin a field selected from the group consisting of the electric fieldand a second electric field, and calculating a second measured parameterof the mammalian luminal organ based in part upon the at least anotherconductance value. In an additional embodiment, the method furthercomprises the step of constructing a profile of the mammalian luminalorgan based in part upon the measured parameter and the second measuredparameter.

In at least one embodiment of a method of using an impedance device ofthe present disclosure, the step of introducing at least part of animpedance device into the mammalian luminal organ comprises introducingthe impedance device selected from the group consisting of an impedancewire and an impedance catheter into the mammalian luminal organ. Inanother embodiment, the method further comprises the following steps tobe performed after the step of obtaining the at least anotherconductance value: moving the first electrode of the impedance device toa third location within the mammalian luminal organ, and obtaining atleast an additional conductance value using the impedance device withina field selected from the group consisting of the electric field, thesecond electric field, and a third electric field, calculating a thirdmeasured parameter of the mammalian luminal organ based in part upon theat least an additional conductance value, and constructing an additionalprofile of the mammalian luminal organ based in part upon the measuredparameter, the second measured parameter, and the third measuredparameter. In yet another embodiment, the method further comprises thestep of inflating a balloon coupled to the impedance device to breakupmaterials causing a stenosis within the mammalian luminal organ. In anadditional embodiment, the method further comprises the step ofimplanting a stent into the mammalian luminal organ by inflating aballoon coupled to the impedance device. In yet an additionalembodiment, the balloon is inflated using a fluid, and wherein themethod further comprises the steps of providing electrical current intothe fluid filling the balloon at various degrees of balloon distension,measuring a conductance of the fluid inside the balloon, and calculatinga cross-sectional area of a balloon lumen.

In at least one embodiment of a method of using an impedance device ofthe present disclosure, the method further comprises the step ofmeasuring a velocity of fluid flow through the mammalian luminal organusing the impedance device. In an additional embodiment, the methodfurther comprises the steps of measuring a first pressure gradient inthe mammalian luminal organ using a pressure transducer coupled to theimpedance device, and calculating a cross-sectional area of themammalian luminal organ based in part on the first pressure gradient. Inyet an additional embodiment, the method further comprises the step ofdetermining a length of a stenosis present within the mammalian luminalorgan based upon the profile.

In at least one embodiment of a method of using an impedance device ofthe present disclosure, the method comprises the steps of introducing atleast part of an impedance device into a mammalian luminal organ at afirst location, the impedance device comprising an elongated body havinga distal body end, and a first electrode located along the elongatedbody at or near the distal body end, the first electrode configured toobtain one or more conductance values within a mammalian luminal organwithin an electric field, providing electrical current to the firstelectrode and a first external electrode not coupled to the elongatedbody to generate the electric field, the first external electrodepositioned upon or within a mammalian body having the mammalian luminalorgan, obtaining at least one conductance value using the impedancedevice within the electric field and within an undiluted bolus of aninjected first solution having a known conductivity differing from ablood conductivity, and calculating a measured parameter of themammalian luminal organ based in part upon the at least one conductancevalue. In another embodiment, the impedance device further comprises asecond electrode positioned along the elongated body, and wherein thestep of obtaining the at least one conductance value is performed usingfirst electrode and the second electrode. In yet another embodiment, theimpedance device further comprises a second electrode and a thirdelectrode each positioned along the elongated body, and wherein the stepof obtaining the at least one conductance value is performed usingsecond electrode and the third electrode.

In at least one embodiment of a method of using an impedance device ofthe present disclosure, the step of obtaining is performed when thefirst electrode is at a first location within the mammalian luminalorgan, and wherein the method further comprises the following steps tobe performed after the step of obtaining the at least one conductancevalue: moving the first electrode of the impedance device to a secondlocation within the mammalian luminal organ, obtaining at least anotherconductance value using the impedance device within a field selectedfrom the group consisting of the electric field and a second electricfield, the step of obtaining the at least another conductance value alsoperformed within a bolus selected from the undiluted bolus of theinjected first solution and an undiluted bolus of an injected secondsolution having a known conductivity differing from the bloodconductivity, and calculating a second measured parameter of themammalian luminal organ based in part upon the at least anotherconductance value. In an additional embodiment, the method furthercomprises the step of constructing a profile of the mammalian luminalorgan based in part upon the measured parameter and the second measuredparameter. In yet an additional embodiment, the step of introducing atleast part of an impedance device into the mammalian luminal organcomprises introducing the impedance device selected from the groupconsisting of an impedance wire and an impedance catheter into themammalian luminal organ. In another embodiment, the method furthercomprises the following steps to be performed after the step ofobtaining the at least another conductance value: moving the firstelectrode of the impedance device to a third location within themammalian luminal organ, and obtaining at least an additionalconductance value using the impedance device within a field selectedfrom the group consisting of the electric field, the second electricfield, and a third electric field, calculating a third measuredparameter of the mammalian luminal organ based in part upon the at leastan additional conductance value, and constructing an additional profileof the mammalian luminal organ based in part upon the measuredparameter, the second measured parameter, and the third measuredparameter. In yet another embodiment, the method further comprises thestep of inflating a balloon coupled to the impedance device to breakupmaterials causing a stenosis within the mammalian luminal organ.

In at least one embodiment of a method of using an impedance device ofthe present disclosure, the method further comprises the steps ofimplanting a stent into the mammalian luminal organ by inflating aballoon coupled to the impedance device. In an additional embodiment,the balloon is inflated using a fluid, and wherein the method furthercomprises the steps of providing electrical current into the fluidfilling the balloon at various degrees of balloon distension, measuringa conductance of the fluid inside the balloon, and calculating across-sectional area of a balloon lumen. In yet an additionalembodiment, the method further comprises the step of measuring avelocity of fluid flow through the mammalian luminal organ using theimpedance device. In another embodiment, the method further comprisesthe steps of measuring a first pressure gradient in the mammalianluminal organ using a pressure transducer coupled to the impedancedevice, and calculating a cross-sectional area of the mammalian luminalorgan based in part on the first pressure gradient. In yet anotherembodiment, the method further comprises the step of determining alength of a stenosis present within the mammalian luminal organ basedupon the profile.

BRIEF DESCRIPTION OF THE DRAWINGS

The disclosed embodiments and other features, advantages, anddisclosures contained herein, and the matter of attaining them, willbecome apparent and the present disclosure will be better understood byreference to the following description of various exemplary embodimentsof the present disclosure taken in conjunction with the accompanyingdrawings, wherein:

FIG. 1A illustrates a balloon catheter having impedance measuringelectrodes supported in front of the stenting balloon;

FIG. 1B illustrates a balloon catheter having impedance measuringelectrodes within and in front of the balloon;

FIG. 1C illustrates a catheter having an ultrasound transducer withinand in front of balloon;

FIG. 1D illustrates a catheter without a stenting balloon;

FIG. 1E illustrates a guide catheter with wire and impedance electrodes;

FIG. 1F illustrates a catheter with multiple detection electrodes;

FIG. 2A illustrates a catheter in cross-section proximal to the locationof the sensors showing the leads embedded in the material of the probe;

FIG. 2B illustrates a catheter in cross-section proximal to the locationof the sensors showing the leads run in separate lumens;

FIG. 3 is a schematic of one embodiment of the system showing a cathetercarrying impedance measuring electrodes connected to the dataacquisition equipment and excitation unit for the cross-sectional areameasurement;

FIG. 4A show the detected filtered voltage drop as measured in the bloodstream before and after injection of 1.5% NaCl solution;

FIG. 4B shows the peak-to-peak envelope of the detected voltage shown inFIG. 4A;

FIG. 5A show the detected filtered voltage drop as measured in the bloodstream before and after injection of 0.5% NaCl solution;

FIG. 5B shows the peak-to-peak envelope of the detected voltage shown inFIG. 5A;

FIG. 6 illustrates balloon distension of the lumen of the coronaryartery;

FIG. 7 illustrates balloon distension of a stent into the lumen of thecoronary artery;

FIG. 8A illustrates the voltage recorded by a conductance catheter witha radius of 0.55 mm for various size vessels (vessel radii of 3.1, 2.7,2.3, 1.9, 1.5 and 0.55 mm for the six curves, respectively) when a 0.5%NaCl bolus is injected into the treatment site;

FIG. 8B illustrates the voltage recorded by a conductance catheter witha radius of 0.55 mm for various size vessels (vessel radii of 3.1, 2.7,2.3, 1.9, 1.5 and 0.55 mm for the six curves, respectively) when a 1.5%NaCl bolus is injected into the treatment site;

FIG. 9 shows a photograph of a segment of swine carotid artery used forperforming ex-vivo validation of the algorithm of the presentdisclosure;

FIG. 10 shows ex-vivo data using a two-injection method of the presentdisclosure;

FIG. 11 shows ex-vivo data using a pull back method of the presentdisclosure; and

FIG. 12 shows in-vivo data using a two-injection method of the presentdisclosure as compared to the IVUS method;

FIG. 13A shows a distal portion of a unipolar device, according to anexemplary embodiment of the present disclosure;

FIG. 13B shows a distal portion of a bipolar device, according to anexemplary embodiment of the present disclosure;

FIG. 13C shows a distal portion of a tripolar device, according to anexemplary embodiment of the present disclosure; and

FIG. 14 shows a block diagram of device and system components andfeatures, according to an exemplary embodiment of the presentdisclosure.

An overview of the features, functions and/or configurations of thecomponents depicted in the various figures will now be presented. Itshould be appreciated that not all of the features of the components ofthe figures are necessarily described. Some of these non-discussedfeatures, such as various couplers, etc., as well as discussed featuresare inherent from the figures themselves. Other non-discussed featuresmay be inherent in component geometry and/or configuration.

DETAILED DESCRIPTION

The disclosure of the present application provides devices, systems, andmethods to obtain accurate measures of the luminal cross-sectional areaof organ stenosis within acceptable limits to enable accurate andscientific stent sizing and placement in order to improve clinicaloutcomes by avoiding under or over deployment and under or over sizingof a stent which can cause acute closure or in-stent re-stenosis. Forthe purposes of promoting an understanding of the principles of thepresent disclosure, reference will now be made to the embodimentsillustrated in the drawings, and specific language will be used todescribe the same. It will nevertheless be understood that no limitationof the scope of the present disclosure is thereby intended.

In one embodiment, an angioplasty or stent balloon includes impedanceelectrodes supported by the catheter in front of the balloon. Theseelectrodes enable the immediate measurement of the cross-sectional areaof the vessel during the balloon advancement. This provides a directmeasurement of non-stenosed area and allows the selection of theappropriate stent size. In one approach, error due to the loss ofcurrent in the wall of the organ and surrounding tissue is corrected byinjection of two solutions of NaCl or other solutions with knownconductivities. In another embodiment impedance electrodes are locatedin the center of the balloon in order to deploy the stent to the desiredcross-sectional area. These embodiments and procedures substantiallyimprove the accuracy of stenting and the outcome and reduce the cost.

Other embodiments make diagnosis of valve stenosis more accurate andmore scientific by providing a direct accurate measurement ofcross-sectional area of the valve annulus, independent of the flowconditions through the valve. Other embodiments improve evaluation ofcross-sectional area and flow in organs like the gastrointestinal tractand the urinary tract.

Embodiments of the disclosure of the present application overcome theproblems associated with determination of the size (cross-sectionalarea) of luminal organs, such as, for example, in the coronary arteries,carotid, femoral, renal and iliac arteries, aorta, gastrointestinaltract, urethra and ureter. Embodiments also provide methods forregistration of acute changes in wall conductance, such as, for example,due to edema or acute damage to the tissue, and for detection of musclespasms/contractions.

As described below, in one preferred embodiment, there is provided anangioplasty catheter with impedance electrodes near the distal end 19 ofthe catheter (i.e., in front of the balloon) for immediate measurementof the cross-sectional area of a vessel lumen during balloonadvancement. This catheter includes electrodes for accurate detection oforgan luminal cross-sectional area and ports for pressure gradientmeasurements. Hence, it is not necessary to change catheters such aswith the current use of intravascular ultrasound. In one preferredembodiment, the catheter provides direct measurement of the non-stenosedarea, thereby allowing the selection of an appropriately sized stent. Inanother embodiment, additional impedance electrodes may be incorporatedin the center of the balloon on the catheter in order to deploy thestent to the desired cross-sectional area. The procedures describedherein substantially improve the accuracy of stenting and improve thecost and outcome as well.

In another embodiment, the impedance electrodes are embedded within acatheter to measure the valve area directly and independent of cardiacoutput or pressure drop and therefore minimize errors in the measurementof valve area. Hence, measurements of area are direct and not based oncalculations with underlying assumptions. In another embodiment,pressure sensors can be mounted proximal and distal to the impedanceelectrodes to provide simultaneous pressure gradient recording.

Devices

Exemplary impedance or conductance catheters for use within thedisclosure of the present application are illustrated in FIGS. 1A-1F.With reference to the exemplary embodiment shown in FIG. 1A, four wireswere threaded through one of the 2 lumens of a 4 Fr catheter. Here,electrodes 26 and 28, are spaced 1 mm apart and form the inner(detection) electrodes. Electrodes 25 and 27 are spaced 4-5 mm fromeither side of the inner electrodes and form the outer (excitation)electrodes. It can be appreciated that catheters of various sizes andincluding electrodes positioned in various locations may be useful inaccordance with the present disclosure.

In one approach, dimensions of a catheter to be used for any givenapplication depend on the optimization of the potential field usingfinite element analysis described below. For small organs, or inpediatric patients the diameter of the catheter may be as small as 0.3mm. In large organs the diameter may be significantly larger dependingon the results of the optimization based on finite element analysis. Theballoon size will typically be sized according to the preferreddimension of the organ after the distension. The balloon may be made ofmaterials, such as, for example, polyethylene, latex,polyestherurethane, or combinations thereof. The thickness of theballoon will typically be on the order of a few microns. The catheterwill typically be made of PVC or polyethylene, though other materialsmay equally well be used. The excitation and detection electrodestypically surround the catheter as ring electrodes but they may also bepoint electrodes or have other suitable configurations. These electrodesmay be made of any conductive material, preferably of platinum iridiumor a carbon-coasted surface to avoid fibrin deposits. In a preferredembodiment, the detection electrodes are spaced with 0.5-1 mm betweenthem and with a distance between 4-7 mm to the excitation electrodes onsmall catheters. The dimensions of the catheter selected for a treatmentdepend on the size of the vessel and are preferably determined in parton the results of finite element analysis, described below. On largecatheters, for use in larger vessels and other visceral hollow organs,the electrode distances may be larger.

Referring to FIGS. 1A, 1B, 1C, and 1D, several embodiments of thecatheters are illustrated. The catheters shown contain to a varyingdegree different electrodes, number and optional balloon(s). Withreference to the embodiment shown in FIG. 1A, there is shown animpedance catheter 20 with 4 electrodes 25, 26, 27, and 28 placed closeto the tip 19 of the catheter. Proximal to these electrodes is anangiography or stenting balloon 30 capable of being used for treatingstenosis. Electrodes 25 and 27 are excitation electrodes, whileelectrodes 26 and 28 are detection electrodes, which allow measurementof cross-sectional area during advancement of the catheter, as describedin further detail below. The portion of the catheter 20 within balloon30 includes an infusion port 35 and a pressure port 36.

The catheter 20 may also advantageously include several miniaturepressure transducers (not shown) carried by the catheter or pressureports for determining the pressure gradient proximal at the site wherethe cross-sectional area is measured. The pressure is preferablymeasured inside the balloon and proximal, distal to and at the locationof the cross-sectional area measurement, and locations proximal anddistal thereto, thereby enabling the measurement of pressure recordingsat the site of stenosis and also the measurement of pressure-differencealong or near the stenosis. In one embodiment, shown in FIG. 1A,catheter 20 advantageously includes pressure port 90 and pressure port91 proximal to or at the site of the cross-sectional measurement forevaluation of pressure gradients. As described below with reference toFIGS. 2A, 2B, and 3, in one embodiment, the pressure ports are connectedby respective conduits in the catheter 20 to pressure sensors in thedata acquisition system 100. Such pressure sensors are well known in theart and include, for example, fiber-optic systems, miniature straingauges, and perfused low-compliance manometry.

In one embodiment, a fluid-filled silastic pressure-monitoring catheteris connected to a pressure transducer. Luminal pressure can be monitoredby a low compliance external pressure transducer coupled to the infusionchannel of the catheter. Pressure transducer calibration was carried outby applying 0 and 100 mmHg of pressure by means of a hydrostatic column.

In one embodiment, shown in FIG. 1B, the catheter 39 includes anotherset of excitation electrodes 40, 41 and detection electrodes 42, 43located inside the angioplastic or stenting balloon 30 for accuratedetermination of the balloon cross-sectional area during angioplasty orstent deployment. These electrodes are in addition to electrodes 25, 26,27, and 28.

In one embodiment, the cross-sectional area may be measured using atwo-electrode system. In another embodiment, illustrated in FIG. 1F,several cross-sectional areas can be measured using an array of 5 ormore electrodes. Here, the excitation electrodes 51, 52, are used togenerate the current while detection electrodes 53, 54, 55, 56, and 57are used to detect the current at their respective sites.

The tip of the catheter can be straight, curved or with an angle tofacilitate insertion into the coronary arteries or other lumens, suchas, for example, the biliary tract. The distance between the balloon andthe electrodes is usually small, in the 0.5-2 cm range but can be closeror further away, depending on the particular application or treatmentinvolved.

In another embodiment, shown in FIG. 1C, the catheter 21 has one or moreimaging or recording devices, such as, for example, ultrasoundtransducers 50 for cross-sectional area and wall thickness measurements.As shown in this embodiment, the transducers 50 are located near thedistal tip 19 of the catheter 21.

FIG. 1D illustrates an embodiment of impedance catheter 22 without anangioplastic or stenting balloon. The catheter in this exemplaryembodiment also possesses an infusion or injection port 35 locatedproximal relative to the excitation electrode 25 and pressure port 36.

With reference to the embodiment shown in FIG. 1E, the electrodes 25,26, 27, and 28 can also be built onto a wire 18, such as, for example, apressure wire, and inserted through a guide catheter 23 where theinfusion of bolus can be made through the lumen of the guide catheter37.

With reference to the embodiments shown in FIGS. 1A, 1B, 1C, 1D, 1E, and1F, the impedance catheter advantageously includes optional ports 35,36, and 37 for suction of contents of the organ or infusion of fluid.The suction/infusion ports 35, 36, and 37 can be placed as shown withthe balloon or elsewhere both proximal or distal to the balloon on thecatheter. The fluid inside the balloon can be any biologicallycompatible conducting fluid. The fluid to inject through the infusionport or ports can be any biologically compatible fluid but theconductivity of the fluid is selected to be different from that of blood(e.g., NaCl).

In another embodiment (not illustrated), the catheter may contain anextra channel for insertion of a guide wire to stiffen the flexiblecatheter during the insertion or data recording. In yet anotherembodiment (not illustrated), the catheter may include a sensor formeasurement of the flow of fluid in the body organ.

System for Determining Cross-Sectional Area and Pressure Gradient

The operation of the impedance catheter 20 is as follows: With referenceto the embodiment shown in FIG. 1A for electrodes 25, 26, 27, and 28,conductance of current flow through the organ lumen and organ wall andsurrounding tissue is parallel; i.e.,

$\begin{matrix}{{G\left( {z,t} \right)} = {\frac{C\; S\;{{A\left( {z,t} \right)} \cdot C_{b}}}{L} + {G_{p}\left( {z,t} \right)}}} & \left\lbrack {1a} \right\rbrack\end{matrix}$where G_(p)(z,t) is the effective conductance of the structure outsidethe bodily fluid (organ wall and surrounding tissue) at a givenposition, z, along the long axis of the organ at a given time, t, andC_(b) is the electrical conductivity of the bodily fluid which for bloodgenerally depends on the temperature, hematocrit and orientation anddeformation of blood cells, and L is the distance between the detectionelectrodes. Equation [1a] can be rearranged to solve for cross sectionalarea CSA(t), with a correction factor, α, if the electric field isnon-homogeneous, as

$\begin{matrix}{{{CSA}\left( {z,t} \right)} = {\frac{L}{\alpha\; C_{b}}\left\lbrack {{G\left( {z,t} \right)} - {G_{p}\left( {z,t} \right)}} \right\rbrack}} & \left\lbrack {1b} \right\rbrack\end{matrix}$where α would be equal to 1 if the field were completely homogeneous.The parallel conductance, G_(p), is an offset error that results fromcurrent leakage. G_(p) would equal 0 if all of the current were confinedto the blood and hence would correspond to the cylindrical model givenby Equation [10]. In one approach, finite element analysis is used toproperly design the spacing between detection and excitation electrodesrelative to the dimensions of the vessel to provide a nearly homogenousfield such that a can be considered equal to 1. Our simulations showthat a homogenous or substantially homogenous field is provided by (1)the placement of detection electrodes substantially equidistant from theexcitation electrodes and (2) maintaining the distance between thedetection and excitation electrodes substantially comparable to thevessel diameter. In one approach, a homogeneous field is achieved bytaking steps (1) and/or (2) described above so that α is equals 1 in theforegoing analysis.

At any given position, z, along the long axis of organ and at any giventime, t, in the cardiac cycle, G_(p) is a constant. Hence, twoinjections of different concentrations and/or conductivities of NaClsolution give rise to two equations:C ₁ ·CSA(z,t)+L·G _(p)(z,t)=L·G ₁(z,t)  [2]andC ₂ ·CSA(z,t)+L·G _(p)(z,t)=L·G ₂(z,t)  [3]which can be solved simultaneously for CSA and G_(p) as

$\begin{matrix}{{{CSA}\left( {z,t} \right)} = {L\frac{\left\lbrack {{G_{2}\left( {z,t} \right)} - {G_{1}\left( {z,t} \right)}} \right\rbrack}{\left\lbrack {C_{2} - C_{1}} \right\rbrack}}} & \lbrack 4\rbrack \\{{G_{p}\left( {z,t} \right)} = \frac{\left\lbrack {{C_{2} \cdot {G_{1}\left( {z,t} \right)}} - {C_{1} \cdot {G_{2}\left( {z,t} \right)}}} \right\rbrack}{\left\lbrack {C_{2} - C_{1}} \right\rbrack}} & \lbrack 5\rbrack\end{matrix}$where subscript “1” and subscript “2” designate any two injections ofdifferent NaCl concentrations and/or conductivities. For each injectionk, C_(k) gives rise to G_(k) which is measured as the ratio of the rootmean square of the current divided by the root mean square of thevoltage. The C_(k) is typically determined through in vitro calibrationfor the various NaCl concentrations and/or conductivities. Theconcentration of NaCl used is typically on the order of 0.45 to 1.8%.The volume of NaCl solution is typically about 5 ml, but sufficient todisplace the entire local vascular blood volume momentarily. The valuesof CSA(t) and G_(p)(t) can be determined at end-diastole or end-systole(i.e., the minimum and maximum values) or the mean thereof.

Once the CSA and G_(p) of the vessel are determined according to theabove embodiment, rearrangement of Equation [1a] allows the calculationof the electrical conductivity of blood in the presence of blood blow as

$\begin{matrix}{C_{b} = {\frac{L}{{CSA}\left( {z,t} \right)}\left\lbrack {{G\left( {z,t} \right)} - {G_{p}\left( {z,t} \right)}} \right\rbrack}} & \lbrack 6\rbrack\end{matrix}$In this way, Equation [1b] can be used to calculate the CSA continuously(temporal variation as for example through the cardiac cycle) in thepresence of blood.

In one approach, a pull or push through is used to reconstruct thevessel along its length. During a long injection (e.g., 10-15 s), thecatheter can be pulled back or pushed forward at constant velocity, U.Equation [1b] can be expressed as

$\begin{matrix}{{{CSA}\left( {{U \cdot t},t} \right)} = {\frac{L}{C_{b}}\left\lbrack {{G\left( {{U \cdot t},t} \right)} - {G_{p}\left( {U \cdot \left( {t,t} \right)} \right\rbrack}} \right.}} & \lbrack 7\rbrack\end{matrix}$where the axial position, z, is the product of catheter velocity, U, andtime, t; i.e., z=U·t.

For the two injections, denoted by subscript “1” and subscript “2”,respectively, different time points T₁, T₂, etc., may be considered suchthat equation [7] can be written as

$\begin{matrix}{{{CSA}_{1}\left( {{U \cdot T_{1}},t} \right)} = {\frac{L}{C_{1}}\left\lbrack {{G_{1}\left( {{U \cdot T_{1}},t} \right)} - {G_{p\; 1}\left( {{U \cdot T_{1}},t} \right)}} \right\rbrack}} & \left\lbrack {8a} \right\rbrack \\{{{{CSA}_{1}\left( {{U \cdot T_{1}},t} \right)} = {\frac{L}{C_{2}}\left\lbrack {{G_{2}\left( {{U \cdot T_{1}},t} \right)} - {G_{p\; 1}\left( {{U \cdot T_{1}},t} \right)}} \right\rbrack}}{and}} & \left\lbrack {8b} \right\rbrack \\{{{CSA}_{2}\left( {{U \cdot T_{2}},t} \right)} = {\frac{L}{C_{1}}\left\lbrack {{G_{1}\left( {{U \cdot T_{2}},t} \right)} - {G_{p\; 2}\left( {{U \cdot T_{2}},t} \right)}} \right\rbrack}} & \left\lbrack {9a} \right\rbrack \\{{{CSA}_{2}\left( {{U \cdot T_{2}},t} \right)} = {\frac{L}{C_{2}}\left\lbrack {{G_{2}\left( {{U \cdot T_{2}},t} \right)} - {G_{p\; 2}\left( {{U \cdot T_{2}},t} \right)}} \right\rbrack}} & \left\lbrack {9b} \right\rbrack\end{matrix}$and so on. Each set of equations [8a], [8b] and [9a], [9b], etc. can besolved for CSA₁, G_(p1) and CSA₂, G_(p2), respectively. Hence, the CSAat various time intervals may be measured and hence of differentpositions along the vessel to reconstruct the length of the vessel. Inone embodiment, the data on the CSA and parallel conductance as afunction of longitudinal position along the vessel can be exported froman electronic spreadsheet, such as, for example, an Excel file, toAutoCAD where the software uses the coordinates to render a profile onthe monitor.

For example, in one exemplary approach, the pull back reconstruction wasmade during a long injection where the catheter was pulled back atconstant rate by hand. The catheter was marked along its length suchthat the pull back was made at 2 mm/sec. Hence, during a 10 secondinjection, the catheter was pulled back about 2 cm. The data wascontinuously measured and analyzed at every two second interval; i.e.,at every 4 mm. Hence, six different measurements of CSA and G_(p) weremade which were used to reconstruct the CSA and G_(p) along the lengthof the 2 cm segment, namely at 0 mm, 4 mm, 8 mm, 12 mm, 16 mm, and 20mm.

Operation of the impedance catheter 39: With reference to the embodimentshown in FIG. 1B, the voltage difference between the detectionelectrodes 42 and 43 depends on the magnitude of the current, I,multiplied by the distance, D, between the detection electrodes anddivided by the conductivity, C, of the fluid and the cross-sectionalarea, CSA, of the artery or other organs into which the catheter isintroduced. Since the current, I, the distance, L, and the conductivity,C, normally can be regarded as calibration constants, an inverserelationship exists between the voltage difference and the CSA as shownby the following equations:

$\begin{matrix}{{\Delta\; V} = {\frac{I \cdot L}{C \cdot {CSA}}\mspace{14mu}{or}}} & \left\lbrack {10a} \right\rbrack \\{{CSA} = \frac{G \cdot L}{C}} & \left\lbrack {10b} \right\rbrack\end{matrix}$where G is conductance expressed as the ratio of current to voltage,I/ΔV. Equation [10] is identical to Equation [1b] if the parallelconductance through the vessel wall is neglected and surrounding tissuebecause the balloon material acts as an insulator. This is thecylindrical model on which the conductance method is used.

As described below with reference to FIGS. 2A, 2B, 3, 4, and 5, theexcitation and detection electrodes are electrically connected toelectrically conductive leads in the catheter for connecting theelectrodes to the data acquisition system 100.

FIGS. 2A and 2B illustrate two embodiments 20A and 20B of the catheterin cross-section. Each embodiment has a lumen 60 for inflating anddeflating the balloon and a lumen 61 for suction and infusion. The sizesof these lumens can vary in size. The impedance electrode electricalleads 70A are embedded in the material of the catheter in the embodimentin FIG. 2A, whereas the electrode electrical leads 70B are tunneledthrough a lumen 71 formed within the body of catheter 70B in FIG. 2B.

Pressure conduits for perfusion manometry connect the pressure ports 90,91 to transducers included in the data acquisition system 100. As shownin FIG. 2A pressure conduits 95A may be formed in 20A. In anotherembodiment, shown in FIG. 2B, pressure conduits 95B constituteindividual conduits within a tunnel 96 formed in catheter 20B. In theembodiment described above where miniature pressure transducers arecarried by the catheter, electrical conductors will be substituted forthese pressure conduits.

With reference to FIG. 3, in one exemplary embodiment, the catheter 20connects to a data acquisition system 100, to a manual or automaticsystem 105 for distension of the balloon and to a system 106 forinfusion of fluid or suction of blood. The fluid will be heated to37-39° or equivalent to body temperature with heating unit 107. Theimpedance planimetry system typically includes a constant current unit,amplifiers and signal conditioners. The pressure system typicallyincludes amplifiers and signal conditioners. The system can optionallycontain signal conditioning equipment for recording of fluid flow in theorgan.

In one preferred embodiment, the system is pre-calibrated and the probeis available in a package. Here, the package also preferably containssterile syringes with the fluids to be injected. The syringes areattached to the machine and after heating of the fluid by the machineand placement of the probe in the organ of interest, the user presses abutton that initiates the injection with subsequent computation of thedesired parameters. The cross-sectional area, CSA, and parallelconductance, G_(p), and other relevant measures such as distensibility,tension, etc. will typically appear on the display panel in the PCmodule 160. Here, the user can then remove the stenosis by distension orby placement of a stent.

If more than one CSA is measured, the system can contain a multiplexerunit or a switch between CSA channels. In one embodiment, each CSAmeasurement will be through separate amplifier units. The same mayaccount for the pressure channels.

In one embodiment, the impedance and pressure data are analog signalswhich are converted by analog-to-digital converters 150 and transmittedto a computer 160 for on-line display, on-line analysis and storage. Inanother embodiment, all data handling is done on an entirely analogbasis. The analysis advantageously includes software programs forreducing the error due to conductance of current in the organ wall andsurrounding tissue and for displaying profile of the CSA distributionalong the length of the vessel along with the pressure gradient. In oneembodiment of the software, a finite element approach or a finitedifference approach is used to derive the CSA of the organ stenosistaking parameters such as conductivities of the fluid in the organ andof the organ wall and surrounding tissue into consideration. In anotherembodiment, simpler circuits are used; e.g., based on making two or moreinjections of different NaCl solutions to vary the resistivity of fluidin the vessel and solving the two simultaneous Equations [2] and [3] forthe CSA and parallel conductance (Equations [4] and [5], respectively).In another embodiment, the software contains the code for reducing theerror in luminal CSA measurement by analyzing signals duringinterventions such as infusion of a fluid into the organ or by changingthe amplitude or frequency of the current from the constant currentamplifier. The software chosen for a particular application, preferablyallows computation of the CSA with only a small error instantly orwithin acceptable time during the medical procedure.

In one approach, the wall thickness is determined from the parallelconductance for those organs that are surrounded by air ornon-conducting tissue. In such cases, the parallel conductance is equalto

$\begin{matrix}{G_{p} = \frac{{CSA}_{w} \cdot C_{w}}{L}} & \left\lbrack {11a} \right\rbrack\end{matrix}$where CSA_(w) is the wall area of the organ and C_(w) is the electricalconductivity through the wall. This equation can be solved for the wallCSA_(w) as

$\begin{matrix}{{CSA}_{w} = \frac{G_{p} \cdot L}{C_{w}}} & \left\lbrack {11b} \right\rbrack\end{matrix}$For a cylindrical organ, the wall thickness, h, can be expressed as

$\begin{matrix}{h = \frac{{CSA}_{w}}{\pi\; D}} & \lbrack 12\rbrack\end{matrix}$where D is the diameter of the vessel which can be determined from thecircular CSA (D=[4CSA/π]^(1/2)).

When the CSA, pressure, wall thickness, and flow data are determinedaccording to the embodiments outlined above, it is possible to computethe compliance (e.g., ΔCSA/ΔP), tension (e.g., P·r, where P and r arethe intraluminal pressure and radius of a cylindrical organ), stress(e.g., P·r/h where h is the wall thickness of the cylindrical organ),strain (e.g., (C−C_(d))/C_(d) where C is the inner circumference andC_(d) is the circumference in diastole) and wall shear stress (e.g., 4μQ/r³ where μ, Q and r are the fluid viscosity, flow rate and radius ofthe cylindrical organ, respectively, for a fully developed flow). Thesequantities can be used in assessing the mechanical characteristics ofthe system in health and disease.

Exemplary Method

In one approach, luminal cross-sectional area is measured by introducinga catheter from an exteriorly accessible opening (e.g., mouth, nose, oranus for GI applications; or e.g., mouth or nose for airwayapplications) into the hollow system or targeted luminal organ. Forcardiovascular applications, the catheter can be inserted into theorgans in various ways; e.g., similar to conventional angioplasty. Inone embodiment, an 18 gauge needle is inserted into the femoral arteryfollowed by an introducer. A guide wire is then inserted into theintroducer and advanced into the lumen of the femoral artery. A 4 or 5Fr conductance catheter is then inserted into the femoral artery viawire and the wire is subsequently retracted. The catheter tip containingthe conductance electrodes can then be advanced to the region ofinterest by use of x-ray (i.e., fluoroscopy). In another approach, thismethodology is used on small to medium size vessels (e.g., femoral,coronary, carotid, iliac arteries, etc.).

In one approach, a minimum of two injections (with differentconcentrations and/or conductivities of NaCl) are required to solve forthe two unknowns, CSA and G_(p). In another approach, three injectionswill yield three set of values for CSA and G_(p) (although notnecessarily linearly independent), while four injections would yield sixset of values. In one approach, at least two solutions (e.g., 0.5% and1.5% NaCl solutions) are injected in the targeted luminal organ orvessel. Our studies indicate that an infusion rate of approximately 1ml/s for a five second interval is sufficient to displace the bloodvolume and results in a local pressure increase of less than 10 mmHg inthe coronary artery. This pressure change depends on the injection ratewhich should be comparable to the organ flow rate.

In one preferred approach, involving the application of Equations [4]and [5], the vessel is under identical or very similar conditions duringthe two injections. Hence, variables, such as, for example, the infusionrate, bolus temperature, etc., are similar for the two injections.Typically, a short time interval is to be allowed (1-2 minute period)between the two injections to permit the vessel to return to homeostaticstate. This can be determined from the baseline conductance as shown inFIG. 4 or 5. The parallel conductance is preferably the same or verysimilar during the two injections. In one approach, dextran, albumin oranother large molecular weight molecule can be added to the NaClsolutions to maintain the colloid osmotic pressure of the solution toreduce or prevent fluid or ion exchange through the vessel wall.

In one approach, the NaCl solution is heated to body temperature priorto injection since the conductivity of current is temperature dependent.In another approach, the injected bolus is at room temperature, but atemperature correction is made since the conductivity is related totemperature in a linear fashion.

In one approach, a sheath is inserted either through the femoral orcarotid artery in the direction of flow. To access the lower anteriordescending (LAD) artery, the sheath is inserted through the ascendingaorta. For the carotid artery, where the diameter is typically on theorder of 5-5.5 mm, a catheter having a diameter of 1.9 mm can be used,as determined from finite element analysis, discussed further below. Forthe femoral and coronary arteries, where the diameter is typically inthe range from 3.5-4 mm, so a catheter of about 0.8 mm diameter would beappropriate. The catheter can be inserted into the femoral, carotid orLAD artery through a sheath appropriate for the particular treatment.Measurements for all three vessels can be made similarly.

Described here are the protocol and results for one exemplary approachthat is generally applicable to most arterial vessels. The conductancecatheter was inserted through the sheath for a particular vessel ofinterest. A baseline reading of voltage was continuously recorded. Twocontainers containing 0.5% and 1.5% NaCl were placed in temperature bathand maintained at 37°. A 5-10 ml injection of 1.5% NaCl was made over a5 second interval. The detection voltage was continuously recorded overa 10 second interval during the 5 second injection. Several minuteslater, a similar volume of 1.5% NaCl solution was injected at a similarrate. The data was again recorded. Matlab was used to analyze the dataincluding filtering with high pass and with low cut off frequency (1200Hz). The data was displayed using Matlab and the mean of the voltagesignal during the passage of each respective solution was recorded. Thecorresponding currents were also measured to yield the conductance,G=I/V. The conductivity of each solution was calibrated with sixdifferent tubes of known CSA at body temperature. A model using Equation[10] was fitted to the data to calculate conductivity C. The analysiswas carried out in SPSS using the non-linear regression fit. Given C andG for each of the two injections, an excel sheet file was formatted tocalculate the CSA and G_(p) as per Equations [4] and [5], respectively.These measurements were repeated several times to determine thereproducibility of the technique. The reproducibility of the data waswithin 5%. Ultrasound (US) was used to measure the diameter of thevessel simultaneous with our conductance measurements. The detectionelectrodes were visualized with US and the diameter measurements wasmade at the center of the detection electrodes. The maximum differencesbetween the conductance and US measurements were within 10%.

FIGS. 4A, 4B, 5A and 5B illustrate voltage measurements in the bloodstream in the left carotid artery. Here, the data acquisition had a thesampling frequency of 75 KHz, with two channels—the current injected andthe detected voltage, respectively. The current injected has a frequencyof 5 KHz, so the voltage detected, modulated in amplitude by theimpedance changing through the bolus injection will have a spectrum inthe vicinity of 5 KHz.

With reference to FIG. 4A, there is shown a signal processed with a highpass filter with low cut off frequency (1200 Hz). The top and bottomportions 200, 202 show the peak-to-peak envelope detected voltage whichis displayed in FIG. 4B (bottom). The initial 7 seconds correspond tothe baseline; i.e., electrodes in the blood stream. The next 7 secondscorrespond to an injection of hyper-osmotic NaCl solution (1.5% NaCl).It can be seen that the voltage is decreased implying increaseconductance (since the injected current is constant). Once the NaClsolution is washed out, the baseline is recovered as can be seen in thelast portion of the FIGS. 4A and 4B. FIGS. 5A and 5B shows similar datacorresponding to 0.5% NaCl solutions.

The voltage signals are ideal since the difference between the baselineand the injected solution is apparent and systematic. Furthermore, thepulsation of vessel diameter can be seen in the 0.5% and 1.5% NaClinjections (FIGS. 4 and 5, respectively). This allows determination ofthe variation of CSA throughout the cardiac cycle as outline above.

The NaCl solution can be injected by hand or by using a mechanicalinjector to momentarily displace the entire volume of blood or bodilyfluid in the vessel segment of interest. The pressure generated by theinjection will not only displace the blood in the antegrade direction(in the direction of blood flow) but also in the retrograde direction(momentarily push the blood backwards). In other visceral organs whichmay be normally collapsed, the NaCl solution will not displace blood asin the vessels but will merely open the organs and create a flow of thefluid. In one approach, after injection of a first solution into thetreatment or measurement site, sensors monitor and confirm baseline ofconductance prior to injection of a second solution into the treatmentsite.

The injections described above are preferably repeated at least once toreduce errors associated with the administration of the injections, suchas, for example, where the injection does not completely displace theblood or where there is significant mixing with blood. It will beunderstood that any bifurcation(s) (with branching angle near 90degrees) near the targeted luminal organ can cause an overestimation ofthe calculated CSA. Hence, generally the catheter should be slightlyretracted or advanced and the measurement repeated. An additionalapplication with multiple detection electrodes or a pull back or pushforward during injection will accomplish the same goal. Here, an arrayof detection electrodes can be used to minimize or eliminate errors thatwould result from bifurcations or branching in the measurement ortreatment site.

In one approach, error due to the eccentric position of the electrode orother imaging device can be reduced by inflation of a balloon on thecatheter. The inflation of balloon during measurement will place theelectrodes or other imaging device in the center of the vessel away fromthe wall. In the case of impedance electrodes, the inflation of ballooncan be synchronized with the injection of bolus where the ballooninflation would immediately precede the bolus injection. Our results,however, show that the error due to catheter eccentricity is small.

The CSA predicted by Equation [4] corresponds to the area of the vesselor organ external to the catheter (i.e., CSA of vessel minus CSA ofcatheter). If the conductivity of the NaCl solutions is determined bycalibration from Equation [10] with various tubes of known CSA, then thecalibration accounts for the dimension of the catheter and thecalculated CSA corresponds to that of the total vessel lumen as desired.In one embodiment, the calibration of the CSA measurement system will beperformed at 37° C. by applying 100 mmHg in a solid polyphenolenoxideblock with holes of known CSA ranging from 7.065 mm² (3 mm in diameter)to 1017 mm² (36 mm in diameter). If the conductivity of the solutions isobtained from a conductivity meter independent of the catheter, however,then the CSA of the catheter is generally added to the CSA computed fromEquation [4] to give the desired total CSA of the vessel.

The signals are generally non-stationary, nonlinear and stochastic. Todeal with non-stationary stochastic functions, one can use a number ofmethods, such as the Spectrogram, the Wavelet's analysis, theWigner-Ville distribution, the Evolutionary Spectrum, Modal analysis, orpreferably the intrinsic model function (IMF) method. The mean orpeak-to-peak values can be systematically determined by theaforementioned signal analysis and used in Equation [4] to compute theCSA.

Exemplary Four-Injection Approach

In at least one method of the disclosure of the present application, afour-injection approach is provided. As previously disclosed herein, twoinjections provide the cross-sectional area, CSA, and parallelconductance, G_(p), at a particular point.

In at least one approach, four injections are provided to determineparallel conductance at multiple points. In an exemplary study, fourinjections may be performed to determine a segment of 2-3 cm long orlonger. In this study, two injections may be performed at the distal endof the segment, and two injections may be performed at the proximal endof the segment. The two injections may deliver, for example, a volume of1.5% NaCl and a volume of 0.5% NaCl, at each end of the segment, notingthat any number of solutions, volumes, and concentrations thereofsuitable for such a study, or for the other studies contemplated by thedisclosure of the present application, could be utilized. For example,solutions having different salinities can be introduced in variousphysiological saline solutions (PSS) or in a Kreb solution containingother ions such as potassium, sodium, etc. In this exemplary study, thefirst two injections (1.5% NaCl and 0.5% NaCl) may be made at the distalpoint of the segment, and the catheter system would then be pulled backto the proximal point of the segment, whereby two more injections (1.5%NaCl and 0.5% NaCl) may be made, with conductance values taken at thedistal end and the proximal end of the segment used to determine theentire profile of the segment.

As referenced herein with respect to Equation [1a], conductance may becalculated taking into account cross-sectional area, electricalconductivity of a fluid, and effective conductance of a structure. Whenperforming a study as described above, the two end points (proximal anddistal ends of a segment) are clearly exact, and an intermediate profilebetween those two points can be derived based upon the analysis providedherein. Since the cross-sectional area, CSA, and parallel conductance ata point, G_(p), are known at each of the two ends of a segment, thecorresponding blood conductivity may be calculated:

$\begin{matrix}{G_{Total} = {\frac{{CSA} \cdot C_{b}}{L} + G_{p}}} & \left\lbrack {13a} \right\rbrack\end{matrix}$where G_(Total) is the total conductance (current divided by voltage),CSA is the cross-sectional area, C_(b) is the blood conductivity, L isthe detection electrode spacing on the catheter, and G_(p) is theparallel conductance at a point. The mean of the two values may then becalculated based upon the foregoing.

A procedure as described above may be accomplished, for example, byperforming the following steps:

-   -   Step 1: Calculate total conductance (G_(Total), current divided        by voltage, or I/V, where I is the current injected and V is the        voltage recorded) for two ends (proximal and distal) of a        segment.    -   Step 2: Calculate the Coeff ratio (cross-sectional area divided        by total conductance, or CSA/G_(Total)) at the two ends of the        segment.    -   Step 3: Linearly interpolate along the length of the pull back        for the Coeff, so that the two ends of the segment have the same        Coeffs calculated from Step 2 above.    -   Step 4: Calculate total conductance (G_(Total)) for the entire        length of the pull back (distance between the two ends of the        segment).    -   Step 5: At each point calculated in the pull back, multiply the        total conductance (G_(Total)) times its respective Coeff. The        product of this calculation is the cross-sectional area (CSA).    -   Step 6: Determine the diameter from the cross-sectional area        (CSA) along the entire profile.

A mathematical explanation of the concept referenced in the procedureabove is as follows. First, the equation governing the physics ofelectrical conductance has the following form:

$\begin{matrix}{G_{Total} = {\frac{I}{V} = {\frac{{CSA} \cdot \sigma}{L} + G_{p}}}} & \lbrack 14\rbrack\end{matrix}$where G_(Total) is the total conductance, I is the current, V is thevoltage, CSA is the cross-sectional area, σ is the conductivity of thefluid, L is the detection electrode spacing on the catheter, and G_(p)is the parallel conductance at a point.

Experimentation as shown that parallel conductance (G_(p)) is linearlyrelated to cross-sectional area, with a negative slope. For example, alarger CSA has a smaller G_(p). As such, G_(p) can be replaced with alinear function of CSA as follows:

$\begin{matrix}{G_{Total} = {\frac{I}{V} = {\frac{{CSA} \cdot \sigma}{L} + {m \cdot {CSA}} + b}}} & \lbrack 15\rbrack\end{matrix}$where G_(Total) is the total conductance, I is the current, V is thevoltage, CSA is the cross-sectional area, σ is the conductivity of thefluid, L is the detection electrode spacing on the catheter, m is theslops, and b is the intercept as can be determined for a linear leastsquare fit. This may be rearranged as follows:

$\begin{matrix}{G_{Total} = {{\left( {\frac{\sigma}{L} + m} \right){CSA}} + b}} & \lbrack 16\rbrack\end{matrix}$

It is shown that total conductance (G_(Total)) is clearly linearlyrelated to cross-sectional area (CSA). If the coefficient b is ignored(wherein b should be equal to zero if CSA is equal to zero), then wehave the following:

$\begin{matrix}{\left( \frac{CSA}{G_{Total}} \right) = {Coeff}} & \lbrack 17\rbrack\end{matrix}$

The Coeff value at both ends of a segment can be found where the twoinjections are made, and those values may then be used to linearlyinterpolate across the profile. Once a Coeff value for every point inthe pull back is determined, those Coeff values are multiplied by theirrespective G_(Total) values to determine the CSA values along theprofile, namely:

$\begin{matrix}{{{CSA} = {{Coeff}*G_{Total}}}{and}} & \lbrack 18\rbrack \\{{Diameter} = \sqrt{\frac{4*{CSA}}{\pi}}} & \lbrack 19\rbrack\end{matrix}$to determine a diameter.Exemplary Three-Injection Approach

In at least one method of the disclosure of the present application, athree-injection approach to determine a profile as outlined above withrespect to the four-injection approach is also provided. In at least oneapproach, three injections are provided, with two injections at thedistal end of a segment, simultaneous withdrawal of one of the injectionsources, and one injection at the proximal end of the segment.

In an exemplary study, the first two injections at the distal end maydeliver, for example, a volume of 1.5% NaCl and a volume of 0.5% NaCl,noting that any number of solutions, volumes, and concentrations thereofsuitable for such a study could be utilized. In this exemplary study,the first two injections (1.5% NaCl and 0.5% NaCl) may be made at thedistal point of the segment, wherein the catheter system issimultaneously withdrawn with the injection of the 0.5% NaCl so that the0.5% NaCl may also be used for the proximal end. These injections wouldthen be followed by a 1.5% NaCl injection at the proximal end of thesegment.

Advantages to this particular approach over the four-injection approachare that (1) the conductivity would be simplified as that of 0.5% ratherthan blood, and (2) there are only three injections required instead offour. However, the three-injection method also requires that a physicianusing a catheter system to perform such a procedure would be required toinject and pull back simultaneously. A physician comfortable withsimultaneous injection and pull back may prefer the three-injectionapproach, while a physician not comfortable with simultaneous injectionand pull back may prefer the four-injection approach. Either approach ispossible using the algorithm provided herein.

Ex-Vivo and In-Vivo Validation of Algorithm

Studies were performed ex-vivo in in-vivo to validate the algorithmprovided herein. The former was validated in a carotid artery with anartificial stenosis to compare the algorithm disclosed herein versuscast measurements for both for the two-injection method at severaldiscrete points and the reconstructed profile. The latter validation wasdone in vivo in a coronary artery (LAD) where a comparison between LR(LumenRecon) and IVUS (intravascular) was made.

Ex-Vivo Validation of Algorithm

To validate the algorithm ex-vivo, a segment of a swine carotid arterywas removed and mounted on a bench stand as shown in FIG. 9. A smallportion of one end of the vessel was removed and used to create astenosis around the vessel, which was accomplished by wrapping thispiece of tissue around the middle of the vessel and shortening the pieceof tissue using suture. A black indicator was used to mark the outsideof the vessel at six locations along the length (length=3.23 cm). Asshown in FIG. 9, the bottom portion of the vessel is the distal end, andblack marks signify where LumenRecon measurements were made using atwo-injection method of the present disclosure.

The LumenRecon system was calibrated using the 0.45% and 1.5% salineconcentrations. A two-injection method according to the presentdisclosure was used to make single diameter measurements at the sixlocations along the length of the vessel. “Pull back” measurements werealso made along the length of the vessel to create a continuous profileof the vessel diameter.

After the LumenRecon measurements were taken, a cast mold of the vesselwas created. The diameter of the cast mold of the vessel was determinedusing microscopy. The cast measurements were taken at the six locationsmarked by the black indicator and at intermediate locations along thevessel.

The diameters from the LumenRecon two injection method and the pull backmeasurements were plotted against the cast measurements, respectively.FIG. 10 shows the data for the six locations using a two-injectionmethod of the present disclosure, comparing the diameters calculated bythe LumenRecon system to those measured from the cast mold of the vesselusing microscopy. The least square fit of the data showsy=1.0599x−0.1805, R²=0.9944. FIG. 11 shows a profile of data points(diameters) using a pull back method of the present disclosure,comparing the diameters calculated by the LumenRecon system to thosemeasured from the cast mold of the vessel using microscopy.

In Vivo Validation

The LumenRecon system was used to make measurements in the left anteriordescending (LAD) coronary artery in an anesthesized swine. Atwo-injection method of the present disclosure was used to construct aprofile which was compared to IVUS at four different locations along theprofile. FIG. 12 shows the LumenRecon measurements plotted against theIVUS measurements, showing the measurements before and after thetemperature correction. The temperature correction was incorporated intothe calibration of the catheter. It was determined that a NaCl solutioninjected at room temperature (25° C.) reaches 30° C. when at the bodysite of measurement (39° C.). Hence, calibrations of fluid were made at30° C. to account for the heating of the fluid during injection.

Referring to the embodiment shown in FIG. 6, the angioplasty balloon 30is shown distended within the coronary artery 150 for the treatment ofstenosis. As described above with reference to FIG. 1B, a set ofexcitation electrodes 40, 41 and detection electrodes 42, 43 are locatedwithin the angioplasty balloon 30. In another embodiment, shown in FIG.7, the angioplasty balloon 30 is used to distend the stent 160 withinblood vessel 150.

For valve area determination, it is not generally feasible to displacethe entire volume of the heart. Hence, the conductivity of blood ischanged by injection of hypertonic NaCl solution into the pulmonaryartery which will transiently change the conductivity of blood. If themeasured total conductance is plotted versus blood conductivity on agraph, the extrapolated conductance at zero conductivity corresponds tothe parallel conductance. In order to ensure that the two innerelectrodes are positioned in the plane of the valve annulus (2-3 mm), inone preferred embodiment, the two pressure sensors 36 are advantageouslyplaced immediately proximal and distal to the detection electrodes (1-2mm above and below, respectively) or several sets of detectionelectrodes (see, e.g., FIGS. 1D and 1F). The pressure readings will thenindicate the position of the detection electrode relative to the desiredsite of measurement (aortic valve: aortic-ventricular pressure; mitralvalve: left ventricular-atrial pressure; tricuspid valve: rightatrial-ventricular pressure; pulmonary valve: rightventricular-pulmonary pressure). The parallel conductance at the site ofannulus is generally expected to be small since the annulus consistsprimarily of collagen which has low electrical conductivity. In anotherapplication, a pull back or push forward through the heart chamber willshow different conductance due to the change in geometry and parallelconductance. This can be established for normal patients which can thenbe used to diagnose valvular stensosis.

In one approach, for the esophagus or the urethra, the procedures canconveniently be done by swallowing fluids of known conductances into theesophagus and infusion of fluids of known conductances into the urinarybladder followed by voiding the volume. In another approach, fluids canbe swallowed or urine voided followed by measurement of the fluidconductances from samples of the fluid. The latter method can be appliedto the ureter where a catheter can be advanced up into the ureter andfluids can either be injected from a proximal port on the probe (willalso be applicable in the intestines) or urine production can beincreased and samples taken distal in the ureter during passage of thebolus or from the urinary bladder.

In one approach, concomitant with measuring the cross-sectional area andor pressure gradient at the treatment or measurement site, a mechanicalstimulus is introduced by way of inflating the balloon or by releasing astent from the catheter, thereby facilitating flow through the stenosedpart of the organ. In another approach, concomitant with measuring thecross-sectional area and or pressure gradient at the treatment site, oneor more pharmaceutical substances for diagnosis or treatment of stenosisis injected into the treatment site. For example, in one approach, theinjected substance can be smooth muscle agonist or antagonist. In yetanother approach, concomitant with measuring the cross-sectional areaand or pressure gradient at the treatment site, an inflating fluid isreleased into the treatment site for release of any stenosis ormaterials causing stenosis in the organ or treatment site.

Again, it will be noted that the methods, systems, and devices describedherein can be applied to any body lumen or treatment site. For example,the methods, systems, and devices described herein can be applied to anyone of the following exemplary bodily hollow systems: the cardiovascularsystem including the heart; the digestive system; the respiratorysystem; the reproductive system; and the urogential tract.

Finite Element Analysis: In one preferred approach, finite elementanalysis (FEA) is used to verify the validity of Equations [4] and [5].There are two major considerations for the model definition: geometryand electrical properties. The general equation governing the electricscalar potential distribution, V, is given by Poisson's equation as:∇·(C∇V)=−I  [13]where C, I, and ∇ are the conductivity, the driving current density, andthe del operator, respectively. Femlab or any standard finite elementpackages can be used to compute the nodal voltages using equation [13].Once V has been determined, the electric field can be obtained from asE=−∇V.

The FEA allows the determination of the nature of the field and itsalteration in response to different electrode distances, distancesbetween driving electrodes, wall thicknesses and wall conductivities.The percentage of total current in the lumen of the vessel, % I, can beused as an index of both leakage and field homogeneity. Hence, thevarious geometric and electrical material properties can be varied toobtain the optimum design; i.e., minimize the non-homogeneity of thefield. Furthermore, the experimental procedure was simulated byinjection of the two solutions of NaCl to verify the accuracy ofEquation [4]. Finally, an assessment of the effect of presence ofelectrodes and catheter in the lumen of vessel may be performed. Theerror terms representing the changes in measured conductance due to theattraction of the field to the electrodes and the repulsion of the fieldfrom the resistive catheter body were quantified.

Poisson's equation for the potential field was solved, taking intoaccount the magnitude of the applied current, the location of thecurrent driving and detection electrodes, and the conductivities andgeometrical shapes in the model including the vessel wall andsurrounding tissue. This analysis suggest that the following conditionsare optimal for the cylindrical model: (1) the placement of detectionelectrodes equidistant from the excitation electrodes; (2) the distancebetween the current driving electrodes should be much greater than thedistance between the voltage sensing electrodes; and (3) the distancebetween the detection and excitation electrodes is comparable to thevessel diameter or the diameter of the vessel is small relative to thedistance between the driving electrodes. If these conditions aresatisfied, the equipotential contours more closely resemble straightlines perpendicular to the axis of the catheter and the voltage dropmeasured at the wall will be nearly identical to that at the center.Since the curvature of the equipotential contours is inversely relatedto the homogeneity of the electric field, it is possible to optimize thedesign to minimize the curvature of the field lines. Consequently, inone preferred approach, one or more of conditions (1)-(3) describedabove are met to increase the accuracy of the cylindrical model.

Theoretically, it is impossible to ensure a completely homogeneous fieldgiven the current leakage through the vessel wall into the surroundingtissue. Research leading to the disclosure of the present applicationidentified that the isopotential line is not constant as one moves outradially along the vessel as stipulated by the cylindrical model. In oneembodiment, a catheter with a radius of 0.55 mm is considered whosedetected voltage is shown in FIGS. 8A and 8B for two different NaClsolutions (0.5% and 1.5%, respectively). The origin corresponds to thecenter of the catheter. The first vertical line 220 represents the innerpart of the electrode which is wrapped around the catheter and thesecond vertical line 221 is the outer part of the electrode in contactwith the solution (diameter of electrode is approximately 0.25 mm). Thesix different curves, top to bottom, correspond to six different vesselswith radii of 3.1, 2.7, 2.3, 1.9, 1.5, and 0.55 mm, respectively. It canbe seen that a “hill” occurs at the detection electrode 220, 221followed by a fairly uniform plateau in the vessel lumen followed by anexponential decay into the surrounding tissue. Since the potentialdifference is measured at the detection electrode 220, 221, thesimulation generates the “hill” whose value corresponds to theequivalent potential in the vessel as used in Eq. [4]. Hence, for eachcatheter size, the dimension of the vessel was varied such that equation[4] is exactly satisfied. Consequently, the optimum catheter size for agiven vessel diameter was obtained such that the distributive modelsatisfies the lumped equations (Equation [4] and [5]). In this way, arelationship between vessel diameter and catheter diameter may begenerated such that the error in the CSA measurement is less than 5%.

In an exemplary embodiment, different diameter catheters are prepackagedand labeled for optimal use in certain size vessel. For example, forvessel dimension in the range of 4-5 mm, 5-7 mm or 7-10 mm, analysis inaccordance with the disclosure of the present application shows that theoptimum diameter catheters will be in the range of 0.9-1.4, 1.4-2.0 or2.0-4.6 mm, respectively. A clinician can select the appropriatediameter catheter based on the estimated vessel diameter of interest.This decision will be made prior to the procedure and will serve tominimize the error in the determination of lumen CSA.

The present disclosure also includes disclosure of impedance deviceshaving one or more electrodes or poles thereon. For device 101 (such as,for example, catheter 20, catheter 20A, catheter 20B, catheter 21,catheter 22, catheter 23, catheter 29, wire 18, and/or other impedancedevice embodiments referenced herein that are configured for use withone, two, three, or potentially more electrodes as described herein),embodiments having only one electrode/pole 102 thereon, therein, orotherwise coupled thereto (hereinafter referred to a “unipolar” devices101), said devices 101 are operable to work with at least one externalelectrode/pole 145 to generate an electric field that can be detected bya detection electrode (another exemplary electrode/pole 102). Device 101embodiments having more than one electrode/pole 102, such as anembodiment having two electrodes/poles 102, three electrodes/poles 102,or four or more electrodes/poles 102, may also be configured andoperable to work with at least one external electrode/pole 102. Forpurposes of the present disclosure, the term “electrode/pole” refers toan electrode or another item operable as a pole, such as a metallicclip, button, pad, sheath, lead, wire, or other item, wherein the itemcan work with another electrode/pole to generate an electric field.Electrodes/poles 102 of the present disclosure may also include one ormore of electrodes 25, 26, 27, 28, 40, 41, 42, 43, 51, 52, 53, 54, 55,56, and/or 57, as generally referenced herein if configured for use inconnection with a particular embodiment.

FIG. 13A shows a distal portion of an exemplary device 101 of thepresent disclosure having one electrode/pole 102 thereon, therein, orotherwise coupled thereto. Such a device 101 is referred to herein as a“unipolar device,” as it has one electrode/pole 102 thereon, therein, orotherwise coupled thereto. Such a device 101, in various embodiments, isused to perform a unipolar method of detection within a mammalian body.

With a unipolar device 101 configuration, and in general, said device101 has a single electrode/pole 102 that has both excitation anddetection functionality. “Excitation,” as referenced herein, refers tothe ability to generate an electric field that a detectionelectrode/pole 102 can detect at least one conductance measurementwithin in connection with one or more methods of the present disclosure.Phrased differently, an electrode/pole 102, in a unipolar device 101embodiment, needs to be able to can excite a field and detect withinsaid field.

Generation of an electric field using a unipolar device 101 embodimentrequires a second electrode/pole 102 positioned somewhere other thandevice 101. For example, a second electrode/pole 102 may comprise partof a patch 130, part of a sheath 140, a clip 145, and/or another itemthat, when used with the electrode/pole 102 of unipolar device 101, canallow for a field to be excited and conductance measurements to beobtained within said field. Should there only be two totalelectrodes/poles 102 (one on device 101 and one not on device 101), bothelectrodes/poles 102 would operate to excite/generate a field and detectwithin a field. If a unipolar device 101 is used in connection with twoadditional items (electrodes/poles 102 and/or items includingelectrodes/poles 102), then the electrode/pole 102 on device 101 wouldstill have excitation and detection functionality, but the other twoelectrodes/poles 102 would not require dual functionality, as long asone electrode/pole 102 can work with the electrode/pole 102 on device101 to excite a field, and as long as another electrode/pole 102 canwork with the electrode/pole 102 on device to detect within the excitedfield.

Devices 101 of the present disclosure can comprise a number ofcomponents/features. For example, devices 101 may be wires or catheters,and thus having an elongated body 104 (such as present with the variousimpedance devices referenced herein) with one or more lumens 175optionally defined therethrough (such as in catheter device 101embodiments). Lumens 175, as referenced herein, may include lumens 60,71, pressure conduit 95A, pressure conduit 95B, and/or tunnel 96, asgenerally referenced herein. Additional components, such as one or moreballoons 30, pressure sensors 110 (which may be a sensor or may beconfigured as a pressure port 36, 90, and/or 91 as generally referencedherein), temperature sensors 112, ablation contacts 114, cuttingportions 116, and/or other components/features known in theintravascular device art thereon, therein, or otherwise coupled thereto.Furthermore, devices 101 may define one or more apertures 118, grooves120, housings 122 (such as to house a balloon 30), suction ports 124(which may be, for example, an infusion port 35, 36, and/or 37, invarious embodiments), and/or vacuum ports 126 therein. FIG. 14 shows ablock component diagram of an exemplary device 101 of the presentdisclosure, wherein device 101 comprises the various componentsreferenced herein. Other device 101 embodiments may have more or lesscomponents than as shown therein. For example, an exemplary unipolardevice 101 embodiment may comprise an elongated body 104 configured as awire, one electrode/pole 102, a temperature sensor 112, and an ablationcontact 114.

A combination of an exemplary device 101 of the present disclosure plusone other component external to the device, such as anotherelectrode/pole 102, a patch 130, a sheath 140, a clip 145, or anotheritem, would comprise an exemplary system 180 of the present disclosure.The component diagram shown in FIG. 14 also shows that an exemplarysystem 180 of the present disclosure can comprise an exemplary device101 of the present disclosure and one or more other components, such asone or more electrodes/poles 102, patches 130, sheaths 140, clips 145,and/or other items. Further, an exemplary system 180 of the presentdisclosure may comprise the use of one or more additional components,such as a second catheter 182 (such as, for example, a guide catheter 23as generally referenced herein), a stent 160, a valve device 206, a lead208, a second wire 210, a needle 212, a diagnostic device 214, and/or atherapeutic device 216, for example. In addition, an exemplary system180 of the present disclosure may comprise a data acquisition andprocessing system 100, a processor 219 (which may be or comprise part ofa computer 160 and/or a data acquisition and processing system 100, invarious embodiments), a storage medium 222, a power source 224, aninjection source 226 (such as, for example, a system 105 or 106 asgenerally referenced herein), and/or a vacuum source 228 (such as, forexample, a system 106 referenced herein). Various components of devices101 and/or systems 180 of the present disclosure may be coupled to oneanother, or otherwise in communication with one another, so to operateas intended, such as through one or more wires 230 (such as, forexample, electrical leads 70A or 70B or other types of wires/leads),tubes 232, and/or connectors 234.

FIG. 13B shows a distal portion of an exemplary device 101 of thepresent disclosure having two electrodes/poles 102 thereon, therein, orotherwise coupled thereto. Such a device 101 is referred to herein as a“bipolar device,” as it has two electrodes/poles 102 thereon, therein,or otherwise coupled thereto. Such a device 101, in various embodiments,is used to perform a bipolar method of detection within a mammalianbody.

Generation of an electric field using a bipolar device 100 can beperformed using the two electrodes/poles 102 thereon, therein, orotherwise coupled thereto, by way of an excitation functionality of saidelectrodes/poles 102. If both electrodes/poles 102 can excite anelectric field and detect within the electric field, only twoelectrodes/poles 102 are required. However, if only one electrode/pole102 can excite an electric field, such an embodiment requires anadditional electrode/pole 102 positioned on device 100 or somewhereother than device 100. For example, an additional electrode/pole 102 maycomprise part of a patch 130, part of a sheath 140, a clip 150, and/oranother item that, when used with one of the electrodes/poles 102 ofbipolar device 100, can allow for a field to be excited and conductancemeasurements to be obtained within said field. Should there only bethree total electrodes/poles 102 (two on device 100 and one not ondevice 100), one electrode/pole on device 100 would operate toexcite/generate a field and detect within a field, and the otherelectrode/pole on device 100 would operate to detect within the field.If a bipolar device 100 is used in connection with two additional items(electrodes/poles 102 and/or items including electrodes/poles 102), thenone electrode/pole 102 on device 100 would be operable to excite a fieldand other would be operable to detect within the field, and one of theelectrodes/poles 102 outside of the device 100 would be operable toexcite a field, and the other electrode/pole outside of device 100 wouldbe operable to detect within the field.

FIG. 13C shows a distal portion of an exemplary device 101 of thepresent disclosure having three electrodes/poles 102 thereon, therein,or otherwise coupled thereto. Such a device 101 is referred to herein asa “tripolar device,” as it has three electrodes/poles 102 thereon,therein, or otherwise coupled thereto. Such a device 101, in variousembodiments, is used to perform a tripolar method of detection within amammalian body.

Generation of an electric field using a tripolar device 100 can beperformed using two electrodes/poles 102 of device 100 by way of anexcitation functionality of said electrodes/poles 102. If twoelectrodes/poles 102 of device can excite an electric field and twoelectrodes/poles 102 of device can excite and detect within the electricfield (where one electrode/pole 102 can excite and detect within thefield), only three electrodes/poles 102 are required. However, if onlyone electrode/pole 102 of device 100 can excite an electric field, suchan embodiment requires an additional electrode/pole 102 positionedsomewhere other than device 100. For example, an additionalelectrode/pole 102 may comprise part of a patch 130, part of a sheath140, a clip 150, and/or another item that, when used with one of theelectrodes/poles 102 of tripolar device 100, can allow for a field to beexcited and conductance measurements to be obtained within said field.In such an embodiment, one electrode/pole 102 on device 100 would beused to excite the field, and the other two electrodes/poles 102 wouldbe used to detect within the field, while the electrode/pole 102 outsideof the device 100 would also be used to excite the field.

A tetrapolar device 101 would include four electrodes/poles 102 ondevice 101, wherein two electrodes/poles 102 (also referred to asexcitation electrodes) would operate to generate a field, while theother two electrodes/poles 102 (also referred to as detectionelectrodes), would be positioned in between the two excitationelectrodes and detect within a field. Such devices are as disclosedwithin U.S. Pat. No. 7,454,244 to Kassab et al., the entire contents ofwhich are hereby incorporated into the present disclosure by reference.Such devices would be used to perform tetrapolar methods, which couldinvolve, in some embodiments, the use of one or more fluid injections(saline, for example), in connection with the performance of the same,as described within said patent.

Conductance measurements obtained using devices 101 and/or systems 180of the present disclosure may use various formulas and/or algorithms,such as Ohm's Law and/or a distance between two electrodes/poles 102used to detect within an electric field, one or more saline injections,etc., as described in one or more of the following references, whereinsaid devices 101 and/or systems are configured to perform one or more ofthe following procedures/tasks:

(a) determining the size (cross-sectional area or diameter, for example)of a mammalian luminal organ, parallel tissue conductance within amammalian luminal organ, and/or navigation of a device within a luminalorgan, such as described within U.S. Pat. No. 7,454,244 to Kassab etal., U.S. Pat. No. 8,114,143 to Kassab et al., U.S. Pat. No. 8,082,032to Kassab et al., U.S. Patent Application Publication No. 2010/0152607of Kassab, U.S. Patent Application Publication No. 2012/0053441 ofKassab, U.S. Patent Application Publication No. 2012/0089046 of Kassabet al., U.S. Patent Application Publication No. 2012/0143078 of Kassabet al., and U.S. Patent Application Publication No. 2013/0030318 ofKassab, the entire contents of which are hereby incorporated into thepresent disclosure by reference;

(b) determining the location of one or more body lumen junctions and/orprofiles of a luminal organ, such as described within U.S. PatentApplication Publication No. 2009/0182287 of Kassab, U.S. PatentApplication Publication No. 2012/0172746 of Kassab, U.S. PatentApplication Publication No. 2010/0010355 of Kassab, and U.S. Pat. No.8,078,274 to Kassab, the entire contents of which are herebyincorporated into the present disclosure by reference;

(c) ablating a tissue within a mammalian patient and/or removingstenotic lesions from a vessel, such as described within U U.S. PatentApplication Publication No. 2009/0182287 of Kassab, U.S. PatentApplication Publication No. 2009/0204134 of Kassab, and U.S. PatentApplication Publication No. 2010/0222786 of Kassab, the entire contentsof which are hereby incorporated into the present disclosure byreference;

(d) determining the existence, potential type, and/or vulnerability of aplaque within a luminal organ, such as described within U.S. PatentApplication Publication No. 2010/0152607 of Kassab, U.S. PatentApplication Publication No. 2011/0034824 of Kassab, and U.S. Pat. No.7,818,053 to Kassab, the entire contents of which are herebyincorporated into the present disclosure by reference;

(e) determining phasic cardiac cycle measurements and determining vesselcompliance, such as described within U.S. Pat. No. 8,185,194 to Kassaband U.S. Pat. No. 8,099,161 to Kassab, the entire contents of which arehereby incorporated into the present disclosure by reference;

(f) determining the velocity of a fluid flowing through a mammalianluminal organ, such as described within U.S. Pat. No. 8,078,274 toKassab, U.S. Patent Application Publication No. 2010/0152607 of Kassab,U.S. Patent Application Publication No. 2012/0053441 of Kassab et al.,and U.S. Patent Application Publication No. 2012/0089046 of Kassab etal., the entire contents of which are hereby incorporated into thepresent disclosure by reference;

(g) sizing of valves using impedance and balloons, such as sizing avalve annulus for percutaneous valves, as described within U.S. PatentApplication Publication No. 2010/0168836 of Kassab, the entire contentsof which are hereby incorporated into the present disclosure byreference;

(h) detecting and/or removing contrast from mammalian luminal organs,such as described within U.S. Pat. No. 8,388,604 to Kassab, the entirecontents of which are hereby incorporated into the present disclosure byreference;

(i) determining fractional flow reserve, such as described within U.S.Patent Application Publication No. 2011/0178417 of Kassab and U.S.Patent Application Publication No. 2011/0178383 of Kassab, the entirecontents of which are hereby incorporated into the present disclosure byreference; and/or

(j) to place leads within a mammalian luminal organ, such as by using adevice 101 of the present disclosure to navigate through a mammalianluminal organ to a location of interest, and using device 101 and/or asecond device to place a lead within said luminal organ.

In addition to the foregoing, various devices 101 of the presentdisclosure, and various other impedance devices as described in one ormore of the aforementioned patents and/or patent applications (such astetrapolar devices), may be operable to perform one or more of thefollowing additional procedures/tasks:

(x) Ablate relatively small veins. Various devices 101 of the presentdisclosure, and various other impedance devices as described in one ormore of the aforementioned patents and/or patent applications (such astetrapolar devices), may be used to navigate through mammalian luminalorgans for Endovascular Laser Therapy (EVLT) for treatment of venousinsufficiency of varicose veins (cosmetic procedures). One objective isto ablate a smaller vein (such as saphenous vein and/or a poplitealvein) as opposed to a larger vein (such as a femoral vein or a commonfemoral vein. EVLT procedures are currently performed within aphysician's office using ultrasound (US) and not fluoroscopy. In obesepatients, the saphenous popliteal junction is difficult to image withUS. As such, a laser catheter (an exemplary or other suitable ablationdevice (such as a device with an ablation contact/portion 114 thereon))is delivered over an impedance wire (an exemplary device 101 of thepresent disclosure or a tetrapolar device as referenced herein), whichmay be, for example, a 0.035″ guidewire. Use of such a device fornavigation (peripherally), one can differentiate (based on a vesselprofile) large from small veins, and also can size the luminal organ inconnection with one or more saline injections, for example), prior toablation, and/or

(y) Navigation for Urological Uses. Various devices 101 of the presentdisclosure, and various other impedance devices as described in one ormore of the aforementioned patents and/or patent applications (such astetrapolar devices), may be used to measure ureter stenosis at differentlevels, including at level of ureter emerging from the kidney, as wellas to measure the urethra/urinary bladder junction, strictures ofabnormal congenital ureter in children, enlargement of ureter inpregnant women due to compression of the uterus against ureter, traumawith pelvic fracture, and other urological conditions. Diagnosis of aurinary obstruction is currently largely established by x-ray studies,noting that the prostate and testis are most vulnerable to x-ray. Thesestudies include kidney x-ray, kidney ultrasound, CAT scan, intravenouspyelogram (IVP) and MRI. Some of these studies may requireadministration of oral or intravenous contrast (dye) and even diureticsdrugs which are painful to the patient and require x-ray exposure. Toovercome these problems, said devices could be used to navigate througha ureter and obtain measurements therein to potentially identify astenosis or other ureter size abnormality.

It can be appreciated that any number of devices may be used inaccordance within the scope of the present disclosure, including, butnot limited to, any number of catheters and/or wires. In exemplaryembodiments, catheters, including, but not limited to, impedance and/orguide catheters, and wires, including, but not limited to, impedancewires, guide wires, pressure wires, and flow wires, may be used asappropriate as devices, systems, and/or portions of systems of thepresent disclosure, and may be used as appropriate to perform one ormore methods, or steps thereof, of the present disclosure.

While various embodiments of impedance devices and methods of using thesame have been described in considerable detail herein, the embodimentsare merely offered as non-limiting examples of the disclosure describedherein. It will therefore be understood that various changes andmodifications may be made, and equivalents may be substituted forelements thereof, without departing from the scope of the presentdisclosure. The present disclosure is not intended to be exhaustive orlimiting with respect to the content thereof.

Further, in describing representative embodiments, the disclosure mayhave presented a method and/or process as a particular sequence ofsteps. However, to the extent that the method or process does not relyon the particular order of steps set forth herein, the method or processshould not be limited to the particular sequence of steps described.Other sequences of steps may be possible. Therefore, the particularorder of the steps disclosed herein should not be construed aslimitations of the present disclosure. In addition, disclosure directedto a method and/or process should not be limited to the performance oftheir steps in the order written. Such sequences may be varied and stillremain within the scope of the present disclosure.

The invention claimed is:
 1. An impedance device, comprising: anelongated body having a distal body end; and a first electrode locatedalong the elongated body at the distal body end, the first electrodeconfigured to obtain one or more conductance values within a mammalianluminal organ within an electric field; wherein the first electrode isconfigured to operate as an excitation electrode and a detectionelectrode; wherein the first electrode is configured to generate theelectric field with an external electrode within a mammalian body whenthe external electrode that is not coupled to the elongated body ispositioned upon or within the mammalian body and when the firstelectrode and the external electrode are activated; wherein the firstelectrode is configured to detect the electric field generated by thefirst electrode and the external electrode; and wherein a measuredparameter of the mammalian luminal organ can be calculated based in partupon the one or more conductance values obtained by the first electrode.2. The impedance device of claim 1, wherein the elongated body isselected from the group consisting of an elongated wire and an elongatedcatheter.
 3. The impedance device of claim 1, further comprising: a dataacquisition and processing system in communication with the impedancedevice and operable to receive and process data from the first electrodeto calculate the measured parameter.
 4. The impedance device of claim 1,further comprising: a pressure sensor configured to detect a pressurewithin the mammalian luminal organ when at least part of the impedancedevice is positioned therein.
 5. The impedance device of claim 1,further comprising: a temperature sensor configured to detect atemperature within the mammalian luminal organ when at least part of theimpedance device is positioned therein.
 6. The impedance device of claim1, further comprising: an ablation contact configured to ablate withinthe mammalian luminal organ when at least part of the impedance deviceis positioned therein.
 7. The impedance device of claim 1, wherein theelongated body is configured as a catheter, and whereby the elongatedbody further defines a suction/infusion port in communication with alumen of the elongated body configured so that a fluid can be injectedthrough the lumen and out of the suction/infusion port.
 8. An impedancesystem, comprising: an elongated body having a distal body end and afirst electrode located along the elongated body at the distal body end,the first electrode configured to obtain one or more conductance valueswithin a mammalian luminal organ within an electric field and configuredto operate as an excitation electrode and a detection electrode; and afirst external electrode that is not coupled to the elongated body;wherein a measured parameter of the mammalian luminal organ can becalculated based in part upon the one or more conductance valuesobtained by the first electrode within the electric field generated bythe first electrode and the first external electrode.
 9. The impedancesystem of claim 8, wherein the first external electrode is configured tooperate as an excitation electrode and a detection electrode.
 10. Thesystem of claim 8, wherein the first external electrode comprises partof device selected from the group consisting of a patch, a sheath, and aclip.
 11. The impedance system of claim 8, wherein the elongated body isselected from the group consisting of an elongated wire and an elongatedcatheter.
 12. The impedance device of claim 8, further comprising: adata acquisition and processing system in communication with theelongated body and operable to receive and process data from the firstelectrode to calculate the measured parameter.
 13. The impedance deviceof claim 8, further comprising: a pressure sensor configured to detect apressure within the mammalian luminal organ when at least part of theelongated body is positioned therein.
 14. The impedance device of claim8, further comprising: a temperature sensor configured to detect atemperature within the mammalian luminal organ when at least part of theelongated body is positioned therein.
 15. The impedance device of claim8, further comprising: an ablation contact configured to ablate withinthe mammalian luminal organ when at least part of the elongated body ispositioned therein.
 16. The impedance device of claim 8, wherein theelongated body is configured as a catheter, and whereby the elongatedbody further defines a suction/infusion port in communication with alumen of the elongated body configured so that a fluid can be injectedthrough the lumen and out of the suction/infusion port.
 17. A method ofusing an impedance device, the method comprising the steps of:introducing at least part of an impedance device into a mammalianluminal organ at a first location, the impedance device comprising: anelongated body having a distal body end, and a first electrode locatedalong the elongated body at the distal body end, the first electrodeconfigured to obtain one or more conductance values within a mammalianluminal organ within an electric field; providing electrical current tothe first electrode and a first external electrode not coupled to theelongated body to generate the electric field, the first externalelectrode positioned upon or within a mammalian body having themammalian luminal organ; obtaining at least one conductance value usingthe impedance device within the electric field, performed when the firstelectrode is at a first location within the mammalian luminal organ andwithin an undiluted bolus of an injected first solution having a knownconductivity differing from a blood conductivity; and calculating ameasured parameter of the mammalian luminal organ based in part upon theat least one conductance value; wherein the method further comprises thefollowing steps to be performed after the step of obtaining the at leastone conductance value: moving the first electrode of the impedancedevice to a second location within the mammalian luminal organ;obtaining at least another conductance value using the impedance devicewithin a field selected from the group consisting of the electric fieldand a second electric field, performed within a bolus selected from theundiluted bolus of the injected first solution and an undiluted bolus ofan injected second solution having a known conductivity differing fromthe blood conductivity; and calculating a second measured parameter ofthe mammalian luminal organ based in part upon the at least anotherconductance value.
 18. The method of claim 17, wherein the measuredparameter is selected from the group consisting of a luminal organdiameter and a luminal organ cross-sectional area.